Cited by 518Cancer, Hypoxia, and MetabolismAdenosine and Purinergic SignalingImmune cells in cancer

The DOI matches its Crossref record; 124 of the 126 references it cites were found in a registry or an index.

Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors

Sitkovsky, Michail, Lukashev, Dmitriy·2005·Nature Reviews Immunology

Open this paper in CoChat — free account

Abstract

Immune cells are often exposed to low oxygen tensions, which markedly affect cellular metabolism. We describe how activated T cells adapt to the changing energy supplies in hypoxic areas of inflamed tissues by using hypoxia-inducible factor 1 (HIF1) to switch to glycolysis as the main source of energy and by signalling through extracellular-adenosine receptors. This hypoxic regulation might alter the balance between T helper 1 cells and T helper 2 cells and might alter the activities of cells of the innate immune system, thereby qualitatively and quantitatively affecting immune responses. This regulatory mechanism should be taken into account in the design and interpretation of in vitro and in vivo studies of immune-cell effector functions.

Integrity signals

Registry

Crossref · 10.1038/nri1685

Cites

124 of 124 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels
Catterall, W. A., Chandy, K. G., Clapham, D. E., Gutman, G. A., Hofmann, F., Harmar, A. J., Abernethy, D. R., & Spedding, M. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.4.5 · Cited by 7,126
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · cited 1×
“, a process that provides long-term T-cell memory and ensures the rapid production of cytokines on subsequent interaction with the pathoge”
Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333
Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent
Babior, B. M., Kipnes, R. S., & Curnutte, J. T. (1973) · Journal of Clinical Investigation · doi:10.1172/jci107236 · Cited by 2,931
A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation
Semenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors
Fredholm, B. B., IJzerman, A. P., Jacobson, K. A., Klotz, K.-N., & Linden, J. (2001) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01511-4 · Cited by 2,585
Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
Carmeliet, P., Dor, Y., Herbert, J.-M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., et al. (1998) · Nature · doi:10.1038/28867 · Cited by 2,502
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
HIF-1α is essential for myeloid cell-mediated inflammation
Cramer, T., Yamanishi, Y., Clausen, B. E., Förster, I., Pawlinski, R., Mackman, N., Haase, V. H., Jaenisch, R., Corr, M., Nizet, V., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00154-5 · Cited by 2,046
Preferential Localization of Effector Memory Cells in Nonlymphoid Tissue
Masopust, D., Vezys, V., Marzo, A. L., & Lefrançois, L. (2001) · Science · doi:10.1126/science.1058867 · Cited by 1,952
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · cited 1×
“One such hypoxia-generated signal could be provided by the mediator of hypoxia HIF1&alpha”
Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892
Lineage relationship and protective immunity of memory CD8 T cell subsets
Wherry, E. J., Teichgräber, V., Becker, T. C., Masopust, D., Kaech, S. M., Antia, R., von Andrian, U. H., & Ahmed, R. (2003) · Nature Immunology · doi:10.1038/ni889 · Cited by 1,864
Interstitial pH and pO2 gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation
Helmlinger, G., Yuan, F., Dellian, M., & Jain, R. K. (1997) · Nature Medicine · doi:10.1038/nm0297-177 · Cited by 1,651
FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor
Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550 · cited 1×
“fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=55662">FIH1 (factor inhibiting HIF1), which inhibits the interaction of HIF1 with either of its co-activators, p300 and CBP (cyclic AMP (cAMP)-responsive-element-binding protein (CREB)-binding protein”
General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.
Wang, G. L., & Semenza, G. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4304 · Cited by 1,468
HIF prolyl‐hydroxylase 2 is the key oxygen sensor setting low steady‐state levels of HIF‐1α in normoxia
Berra, E., Benizri, E., Ginouvès, A., Volmat, V., Roux, D., & Pouysségur, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg392 · Cited by 1,348
Oxidative Phosphorylation at the fin de siècle
Saraste, M. (1999) · Science · doi:10.1126/science.283.5407.1488 · Cited by 1,345
Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage
Ohta, A., & Sitkovsky, M. V. (2001) · Nature · doi:10.1038/414916a · Cited by 1,336
Self-citation
Cellular adaptation to hypoxia: O 2 ‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O 2 ‐regulated gene expression
Wenger, R. H. (2002) · The FASEB Journal · doi:10.1096/fj.01-0944rev · Cited by 1,135
Differential Function of the Prolyl Hydroxylases PHD1, PHD2, and PHD3 in the Regulation of Hypoxia-inducible Factor
Appelhoff, R. J., Tian, Y.-M., Raval, R. R., Turley, H., Harris, A. L., Pugh, C. W., Ratcliffe, P. J., & Gleadle, J. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406026200 · Cited by 1,108
Oncogenic alterations of metabolism
Dang, C. V., & Semenza, G. L. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01344-9 · Cited by 1,106
Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth
Maxwell, P. H., Dachs, G. U., Gleadle, J. M., Nicholls, L. G., Harris, A. L., Stratford, I. J., Hankinson, O., Pugh, C. W., & Ratcliffe, P. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8104 · Cited by 1,084
Visualizing the generation of memory CD4 T cells in the whole body
Reinhardt, R. L., Khoruts, A., Merica, R., Zell, T., & Jenkins, M. K. (2001) · Nature · doi:10.1038/35065111 · Cited by 1,026 · cited 1×
“For example, antigen-specific T cells are exposed to different oxygen tensions as they clonally expand in secondary lymphoid organs, then migrate and reside in non-lymphoid tissues during infection”
Hypoxia-induced neutrophil survival is mediated by HIF-1α–dependent NF-κB activity
Walmsley, S. R., Print, C., Farahi, N., Peyssonnaux, C., Johnson, R. S., Cramer, T., Sobolewski, A., Condliffe, A. M., Cowburn, A. S., Johnson, N., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040624 · Cited by 891
Akt Promotes Survival of Cardiomyocytes In Vitro and Protects Against Ischemia-Reperfusion Injury in Mouse Heart
Fujio, Y., Nguyen, T. U., Wencker, D., Kitsis, R. N., & Walsh, K. (2000) · Circulation · doi:10.1161/01.cir.101.6.660 · Cited by 846
p42/p44 Mitogen-activated Protein Kinases Phosphorylate Hypoxia-inducible Factor 1α (HIF-1α) and Enhance the Transcriptional Activity of HIF-1
Richard, D. E., Berra, E., Gothié, E., Roux, D., & Pouysségur, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.46.32631 · Cited by 797
Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia
Synnestvedt, K., Furuta, G. T., Comerford, K. M., Louis, N. A., Karhausen, J., Eltzschig, H. K., Hansen, K. R., Thompson, L. F., & Colgan, S. P. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15337 · Cited by 706
P hysiological C ontrol of I mmune R esponse and I nflammatory T issue D amage by H ypoxia -I nducible F actors and A denosine A 2A R eceptors
Sitkovsky, M. V., Lukashev, D. E., Apasov, S. G., Kojima, H., Koshiba, M., Caldwell, C. C., Ohta, A., & Thiel, M. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104731 · Cited by 697
Self-citation
Molecular Approach to Adenosine Receptors: Receptor-Mediated Mechanisms of Tissue Protection
Linden, J. M. (2001) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.775 · Cited by 681
Ecto-5′-Nucleotidase (CD73) Regulation by Hypoxia-Inducible Factor-1 Mediates Permeability Changes in Intestinal Epithelia
Synnestvedt, K., Furuta, G. T., Comerford, K. M., Louis, N., Karhausen, J., Eltzschig, H. K., Hansen, K. R., Thompson, L. F., & Colgan, S. P. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215337 · Cited by 660
Non-hypoxic pathway mediates the induction of hypoxia inducible factor 1 alpha (HIF-1 alpha ) in vascular smooth muscle cells
Richard, D. E., Berra, E., & Pouysségur, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003325200 · Cited by 635
Insulin induces transcription of target genes through the hypoxia‐inducible factor HIF‐1α/ARNT
Zelzer, E., Levy, Y., Kahana, C., Shilo, B., Rubinstein, M., & Cohen, B. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5085 · Cited by 574
Cellular Mechanism of Oxygen Sensing
López‐Barneo, J., Pardal, R., & Ortega‐Sáenz, P. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.259 · Cited by 551
Crucial Role for Ecto-5′-Nucleotidase (CD73) in Vascular Leakage during Hypoxia
Thompson, L. F., Eltzschig, H. K., Ibla, J. C., Wiele, C. J. V. D., Resta, R., Morote–Garcia, J. C., & Colgan, S. P. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040915 · Cited by 544
Role of A2a Extracellular Adenosine Receptor-Mediated Signaling in Adenosine-Mediated Inhibition of T-Cell Activation and Expansion
Huang, S., Apasov, S., Koshiba, M., & Sitkovsky, M. (1997) · Blood · doi:10.1182/blood.v90.4.1600 · Cited by 531
Self-citation
Energy Metabolism of Human Neutrophils during Phagocytosis
Borregaard, N., & Herlin, T. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110647 · Cited by 503
Suppression of tumor growth through disruption of hypoxia-inducible transcription
Kung, A. L., Wang, S., Klco, J. M., Kaelin, W. G., & Livingston, D. M. (2000) · Nature Medicine · doi:10.1038/82146 · Cited by 502
Induction of Vascular Endothelial Growth Factor by Hypoxia Is Modulated by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Ha-ras-Transformed Cells Through a Hypoxia Inducible Factor-1 Transcriptional Element
Mazure, N. M., Chen, E. Y., Laderoute, K. R., & Giaccia, A. J. (1997) · Blood · doi:10.1182/blood.v90.9.3322 · Cited by 500
In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability
Rathmell, J. C., Heiden, M. G. V., Harris, M. H., Frauwirth, K. A., & Thompson, C. B. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00066-6 · Cited by 467
Intracellular localisation of human HIF-1α hydroxylases:implications for oxygen sensing
Metzen, E., Berchner-Pfannschmidt, U., Stengel, P., Marxsen, J. H., Stolze, I., Klinger, M., Huang, W. Q., Wotzlaw, C., Hellwig-Bürgel, T., Jelkmann, W., et al. (2003) · Journal of Cell Science · doi:10.1242/jcs.00318 · Cited by 432
The respiratory burst of phagocytic cells is associated with a rise in vacuolar pH
Segal, A. W., Geisow, M. J., Garcia, R. C., Harper, A., & Miller, R. F. (1981) · Nature · doi:10.1038/290406a0 · Cited by 422
Differential Effects of Physiologically Relevant Hypoxic Conditions on T Lymphocyte Development and Effector Functions
Caldwell, C. C., Kojima, H., Lukashev, D., Armstrong, J., Farber, M., Apasov, S. G., & Sitkovsky, M. V. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.11.6140 · Cited by 420
Self-citation
Nitric Oxide Impairs Normoxic Degradation of HIF-1α by Inhibition of Prolyl Hydroxylases
Metzen, E., Zhou, J., Jelkmann, W., Fandrey, J., & Brüne, B. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-12-0791 · Cited by 414
Siah2 Regulates Stability of Prolyl-Hydroxylases, Controls HIF1α Abundance, and Modulates Physiological Responses to Hypoxia
Nakayama, K., Frew, I. J., Hagensen, M. K., Skals, M., Habelhah, H., Bhoumik, A., Kadoya, T., Erdjument‐Bromage, H., Tempst, P., Frappell, P. B., et al. (2004) · Cell · doi:10.1016/j.cell.2004.06.001 · Cited by 406
Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species 1
Brand, K. A., & Hermfisse, U. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.5.9141507 · Cited by 401
A2A Adenosine Receptor Induction Inhibits IFN-γ Production in Murine CD4+ T Cells
Lappas, C. M., Rieger, J. M., & Linden, J. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.2.1073 · Cited by 384
The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that promote chemotaxis and inhibit O2 generation, respectively.
Cronstein, B. N., Daguma, L., Nichols, D., Hutchison, A. J., & Williams, M. J. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114547 · Cited by 376
Heterogeneous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma.
Vaupel, P. W., Frinak, S., & Bicher, H. I. (1981) · PubMed · Cited by 337
Aerobic glycolysis during lymphocyte proliferation
Wang, T., Marquardt, C. A., & Foker, J. E. (1976) · Nature · doi:10.1038/261702a0 · Cited by 333
CD4 Effector T Cell Subsets in the Response to Influenza
Román, E., Miller, E., Harmsen, A. G., Wiley, J., von Andrian, U. H., Huston, G. E., & Swain, S. L. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20021052 · Cited by 327
THE EFFECTS OF INJURY ON THE ADAPTIVE IMMUNE RESPONSE
Lederer, J. A., Rodrick, M. L., & Mannick, J. A. (1999) · Shock · doi:10.1097/00024382-199903000-00001 · Cited by 309
Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production.
Greiner, E. F., Guppy, M., & Brand, K. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31720-4 · Cited by 307
Glycolysis, glutaminolysis and cell proliferation
McKeehan, W. L. (1982) · Cell Biology International Reports · doi:10.1016/0309-1651(82)90125-4 · Cited by 305
Oxygenation Inhibits the Physiological Tissue-Protecting Mechanism and Thereby Exacerbates Acute Inflammatory Lung Injury
Thiel, M., Choukèr, A., Ohta, A., Jackson, E., Caldwell, C. C., Smith, P. T., Lukashev, D. E., Bittmann, I., & Sitkovsky, M. V. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030174 · Cited by 287
Self-citation
Comparison of tumor and normal tissue oxygen tension measurements using OxyLite or microelectrodes in rodents
Braun, R. D., Lanzen, J. L., Snyder, S. A., & Dewhirst, M. W. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.6.h2533 · Cited by 285
Normoxic induction of the hypoxia‐inducible factor 1α by insulin and interleukin‐1β involves the phosphatidylinositol 3‐kinase pathway
Stiehl, D. P., JELKMANN, W. E. B., Wenger, R. H., & Hellwig‐Bürgel, T. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02247-0 · Cited by 284
Bioenergetics of immune functions: fundamental and therapeutic aspects
Buttgereit, F., Burmester, G. R., & Brand, M. D. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01593-0 · Cited by 284
Secretion of pyruvate. An antioxidant defense of mammalian cells.
O’Donnell-Tormey, J., Nathan, C. F., Lanks, K. W., DeBoer, C. J., & de la Harpe, J. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.165.2.500 · Cited by 281
Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha.
Welsh, S. J., Williams, R. R., Kirkpatrick, L., Paine-Murrieta, G. D., & Powis, G. (2004) · PubMed · Cited by 280
Oxygen in mammalian tissue: methods of measurement and affinities of various reactions
Vanderkooi, J. M., Erecińska, M., & Silver, I. A. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.260.6.c1131 · Cited by 279
Hypoxia-Induced Inhibition of Adenosine Kinase Potentiates Cardiac Adenosine Release
Decking, U. K. M., Schlieper, G., Kroll, K., & Schrader, J. (1997) · Circulation Research · doi:10.1161/01.res.81.2.154 · Cited by 267
Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells
Ghezzi, P., Dinarello, C. A., Bianchi, M., Rosandich, M. E., Repine, J. E., & White, C. W. (1991) · Cytokine · doi:10.1016/1043-4666(91)90015-6 · Cited by 260
Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of β 2 integrin gene expression
Kong, T., Eltzschig, H. K., Karhausen, J., Colgan, S. P., & Shelley, C. S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401339101 · Cited by 242
The effect of Hydrocortisone on the kinetics of normal human lymphocytes
Fauci, A. S., & Dale, D. (1975) · Blood · doi:10.1182/blood.v46.2.235.235 · Cited by 236
Respiratory gas tensions and pH in healing wounds
Hunt, T. K., Twomey, P. L., Zederfeldt, B., & Dunphy, J. E. (1967) · The American Journal of Surgery · doi:10.1016/0002-9610(67)90388-1 · Cited by 229
Adenosine affects expression of membrane molecules, cytokine and chemokine release, and the T-cell stimulatory capacity of human dendritic cells
Panther, E., Corinti, S., Idzko, M., Herouy, Y., Napp, M., la Sala, A., Girolomoni, G., & Norgauer, J. (2003) · Blood · doi:10.1182/blood-2002-07-2113 · Cited by 229
Identification of a Novel Small-Molecule Inhibitor of the Hypoxia-Inducible Factor 1 Pathway
Tan, C., de Noronha, R. G., Roecker, A. J., Pyrzyńska, B., Khwaja, F. W., Zhang, Z., Zhang, H., Teng, Q., Nicholson, A. C., Giannakakou, P., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.605.65.2 · Cited by 226
Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1α-deficient chimeric mice
Kojima, H., Gu, H., Nomura, S., Caldwell, C. C., Kobata, T., Carmeliet, P., Semenza, G. L., & Sitkovsky, M. V. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052706699 · Cited by 224
Self-citation
OS-9 Interacts with Hypoxia-Inducible Factor 1α and Prolyl Hydroxylases to Promote Oxygen-Dependent Degradation of HIF-1α
Baek, J. H., Mahon, P. C., Oh, J. C., Kelly, B., Krishnamachary, B., Pearson, M., Chan, D. A., Giaccia, A. J., & Semenza, G. L. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.01.011 · Cited by 218
Interleukin 1 induces hypoxia-inducible factor 1 in human gingival and synovial fibroblasts
Thornton, R. D., Lane, P., Borghaei, R. C., Pease, E. A., Jaime, C. A. R. O., & Mochan, E. (2000) · Biochemical Journal · doi:10.1042/bj3500307 · Cited by 216
Memory of Extracellular Adenosine A2A Purinergic Receptor-mediated Signaling in Murine T Cells
Koshiba, M., Kojima, H., Huang, S. C., Apasov, S. G., & Sitkovsky, M. V. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.41.25881 · Cited by 189
Self-citation
Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes
Roos, D., & Loos, J. A. (1973) · Experimental Cell Research · doi:10.1016/0014-4827(73)90561-2 · Cited by 182
Aerobic glycolysis and lymphocyte transformation
Hume, D. A., Radik, J., Ferber, E., & Weidemann, M. J. (1978) · Biochemical Journal · doi:10.1042/bj1740703 · Cited by 176
Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells
Makino, Y., Nakamura, H., Ikeda, E., Ohnuma, K., Yamauchi, K., Yabe, Y., Poellinger, L., Okada, Y., Morimoto, C., & Tanaka, H. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.12.6534 · Cited by 159
Concepts of oxygen transport at the microcirculatory level
Dewhirst, M. W. (1998) · Seminars in Radiation Oncology · doi:10.1016/s1053-4296(98)80040-4 · Cited by 155
Cutting Edge: Physiologic Attenuation of Proinflammatory Transcription by the Gs Protein-Coupled A2A Adenosine Receptor In Vivo
Lukashev, D. E., Ohta, A., Apasov, S. G., Chen, J., & Sitkovsky, M. V. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.1.21 · Cited by 153
Self-citation
The Repertoires of Circulating Human CD8+ Central and Effector Memory T Cell Subsets Are Largely Distinct
Baron, V. T., Bouneaud, C., Cumano, A., Lim, A., Arstila, T. P., Kourilsky, P., Ferradini, L., & Pannetier, C. (2003) · Immunity · doi:10.1016/s1074-7613(03)00020-7 · Cited by 149
Signaling Takes a Breath – New Quantitative Perspectives on Bioenergetics and Signal Transduction
Krauss, S., Brand, M. D., & Buttgereit, F. (2001) · Immunity · doi:10.1016/s1074-7613(01)00205-9 · Cited by 147
Formation and release of purine catabolites during hypoperfusion, anoxia, and ischemia
Belle, H. V., Goossens, F., & Wynants, J. (1987) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1987.252.5.h886 · Cited by 140
Regulation by Neurotransmitter Receptors of Serotonergic or Catecholaminergic Neuronal Cell Differentiation
Mouillet‐Richard, S., Mutel, V., Loric, S., Tournois, C., Launay, J., & Kellermann, O. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.13.9186 · Cited by 130
Chronic Hypoxia Enhances Adenosine Release in Rat PC12 Cells by Altering Adenosine Metabolism and Membrane Transport
Kobayashi, S., Zimmermann, H., & Millhorn, D. E. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.740621.x · Cited by 128
Differential requirement for A2a and A3 adenosine receptors for the protective effect of inosine in vivo
Gomez, G., & Sitkovsky, M. V. (2003) · Blood · doi:10.1182/blood-2002-11-3624 · Cited by 124
Self-citation
Glycobiology and Cancer: Meeting Summary and Future Directions
Hart, G. W., Lowe, J. B., & Sathyamoorthy, N. (2004) · Cancer Biology & Therapy · doi:10.4161/cbt.3.2.775 · Cited by 122
Chemotactic factor‐induced generation of superoxide radicals by human neutrophils
Simchowitz, L., Mehta, J., & Spilberg, I. (1979) · Arthritis & Rheumatism · doi:10.1002/art.1780220711 · Cited by 121
Hypoxia Regulates Expression and Activity of Kv1.3 Channels in T Lymphocytes: A Possible Role in T Cell Proliferation
Conforti, L., Petrovic, M., Mohammad, D., Lee, S., Ma, Q., Barone, S., & Filipovich, A. H. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.2.695 · Cited by 118
Hypoxia Induces a Human Macrophage Cell Line to Release Tumor Necrosis Factor-α and Its Soluble Receptors in Vitro
Scannell, G., Waxman, K., Kaml, G. J., Ioli, G. R., Gatanaga, T., Yamamoto, R. S., & Granger, G. A. (1993) · Journal of Surgical Research · doi:10.1006/jsre.1993.1044 · Cited by 114
Vhlh Gene Deletion Induces Hif-1-Mediated Cell Death in Thymocytes
Biju, M. P., Neumann, A. K., Bensinger, S. J., Johnson, R. S., Turka, L. A., & Haase, V. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.9038-9047.2004 · Cited by 111
Changes in the carbohydrate metabolism of mitogenically stimulated human peripheral lymphocytes. 3. Stimulation by tuberculin and allogeneic cells.
Loos, J. A., & Roos, D. (1973) · PubMed · Cited by 107
Analysis of pH, pO2 and pCO2 in drainage fluid allows for rapid detection of infectious complications during the follow-up period after abdominal surgery
Simmen, H., Battaglia, H., Giovanoli, P., & Blaser, J. (1994) · Infection · doi:10.1007/bf01715494 · Cited by 100
Differential Regulation of Two Alternatively Spliced Isoforms of Hypoxia-inducible Factor-1α in Activated T Lymphocytes
Lukashev, D. E., Caldwell, C. C., Ohta, A., Chen, P., & Sitkovsky, M. V. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104782200 · Cited by 97
Self-citation
Analysis of A2a receptor-deficient mice reveals no significant compensatory increases in the expression of A2b, A1, and A3 adenosine receptors in lymphoid organs
Lukashev, D. E., Smith, P. T., Caldwell, C. C., Ohta, A., Apasov, S. G., & Sitkovsky, M. V. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00158-8 · Cited by 80
Self-citation
Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine
Mongan, P. D., Capacchione, J. F., West, S., Karaian, J., Dubois, D., Keneally, R. J., & Sharma, P. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01073.2001 · Cited by 80
Mouse Hypoxia-Inducible Factor-1α Is Encoded by Two Different mRNA Isoforms: Expression From a Tissue-Specific and a Housekeeping-Type Promoter
Wenger, R. H., Rolfs, A., Spielmann, P., Zimmermann, D. R., & Gassmann, M. (1998) · Blood · doi:10.1182/blood.v91.9.3471 · Cited by 75
RNA interference for HIF-1α inhibits its downstream signalling and affects cellular proliferation
Hänze, J., Eul, B. G., Savai, R., Krick, S., Goyal, P., Grimminger, F., Seeger, W., & Rose, F. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.10.153 · Cited by 72
Distinct aerobic and hypoxic mechanisms of HIF-α regulation by CSN5Preprint
Bemis, L., Chan, D. A., Finkielstein, C. V., Qi, L., Sutphin, P. D., Chen, X., Stenmark, K. R., Giaccia, A. J., & Zundel, W. (2004) · Genes & Development · doi:10.1101/gad.1180104 · Cited by 71
Hypoxia modulates early events in T cell receptor‐mediated activation in human T lymphocytes via Kv1.3 channels
Robbins, J. R., Lee, S. M., Filipovich, A. H., Szigligeti, P., Neumeier, L., Petrovic, M., & Conforti, L. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.081893 · Cited by 67
THE ACTION OF LEUCOCYTES ON GLUCOSE
Levene, P. A., & Meyer, G. M. (1912) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)88742-7 · Cited by 66
Effects of Space Cabin Environment on Resistance to Infection I. Effect of 18,000-Foot Altitude on Resistance to Respiratory Infection
Ehrlich, R. M., & Mieszkuc, B. J. (1962) · The Journal of Infectious Diseases · doi:10.1093/infdis/110.3.278 · Cited by 63
Effects of hypoxia on interleukin-2 mRNA expression by T lymphocytes
Zuckerberg, A. L., Goldberg, L. I., & Lederman, H. M. (1994) · Critical Care Medicine · doi:10.1097/00003246-199402000-00008 · Cited by 60
Energy metabolism and T-cell-mediated cytolysis. I. Synergism between inhibitors of respiration and glycolysis.
MacDonald, H. R., & Koch, C. J. (1977) · The Journal of Experimental Medicine · doi:10.1084/jem.146.3.698 · Cited by 60
Inflammatory mediators are perpetuated in macrophages resistant to apoptosis induced by hypoxia
Yun, J. K., McCormick, T. S., Villabona, C., Judware, R., Espinosa, M. B., & Lapetina, E. G. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.25.13903 · Cited by 58
Interstitial Transudate Purines in Normoxic and Hypoxic Immature and Mature Rabbit Hearts
Matherne, G. P., Headrick, J. P., Coleman, S. D., & Berne, R. M. (1990) · Pediatric Research · doi:10.1203/00006450-199010000-00010 · Cited by 52
Influence of Inhibitors of Cellular Function on Chemotactic Factor-Induced Neutrophil Aggregation
O’Flaherty, J. T., Kreutzer, D. L., Showell, H. J., & Ward, P. A. (1977) · The Journal of Immunology · doi:10.4049/jimmunol.119.5.1751 · Cited by 52
Wound healing: the effect of macrophage and tumour derived angiogenesis factors on skin graft vascularization.
Arnold, F., West, D. C., & Kumar, S. (1987) · PubMed · Cited by 47
Genetic control of oxidative phosphorylation and experimental models of defects
Trounce, I. A. (2000) · Human Reproduction · doi:10.1093/humrep/15.suppl_2.18 · Cited by 44
Effects of high altitude stay on the incidence of common diseases in man
Singh, I., Chohan, I. S., Lal, M., Khanna, P. K., Srivastava, M. C., Nanda, R. B., Lamba, J. S., & Malhotra, M. S. (1977) · International Journal of Biometeorology · doi:10.1007/bf01553705 · Cited by 42
Lymphocytic infiltration and cytotoxicity under hypoxic conditions in the EMT6 mouse mammary tumor
Loeffler, D. A., Keng, P. C., Baggs, R. B., & Lord, E. M. (1990) · International Journal of Cancer · doi:10.1002/ijc.2910450315 · Cited by 39
Phagocytosis and ATP Levels in Alveolar Macrophages during Acute Hypoxia
Leeper-Woodford, S. K., & Mills, J. W. (1992) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb/6.3.326 · Cited by 38
Effects of Trauma on Leukocyte Intercellular Adhesion Molecule-1, CD11b, and CD18 Expressions
Scannell, G., Waxman, K., Vaziri, N. D., Zhang, J., Kaupke, C. J., Jalali, M., & Hect, C. (1995) · doi:10.1097/00005373-199510000-00004 · Cited by 36
Role of oxygen in T cell-mediated cytolysis.
Nathan, C., Mercer-Smith, J. A., Desantis, N. M., & Palladino, M. A. (1982) · The Journal of Immunology · doi:10.4049/jimmunol.129.5.2164 · Cited by 32
A New Method for the Production of Experimental Bacterial Endocarditis
Highman, B., & Altland, P. D. (1950) · Experimental Biology and Medicine · doi:10.3181/00379727-75-18270 · Cited by 25
Respiratory GAS Exchange and pO2- Distribution in Splenic Tissue
Vaupel, P., Braunbeck, W., & Thews, G. (1973) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-3288-6_50 · Cited by 14
Expression of HIF-1 and ubiquitin in conventional renal cell carcinoma
Hughson, M. D., He, Z., Liu, S., Coleman, J. P., & Shingleton, W. B. (2003) · Cancer Genetics and Cytogenetics · doi:10.1016/s0165-4608(02)00856-7 · Cited by 12
A protective effect of glucocorticoids in hypoxic stress
ROOSEVELT, T. S., Ruhmann‐Wennhold, A., & Nelson, D. (1972) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1972.223.1.30 · Cited by 11
Influence of simulated altitude on resistance-susceptibility to S. typhimurium infection in mice.
Lj, B., & Rb, M. (1953) · PubMed · Cited by 11
Measurement of Local Po2 and Intracapillary Hemoglobin Oxygenation in Lung Tissue of Rabbits
Volkholz, H., Höper, J., Brunner, M., Frank, K. H., Harrison, D. K., Ellermann, R., & Kessler, M. D. (1984) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-1188-1_57 · Cited by 6
Parabarosis and experimental infections. 4. Effect of varying 02 tensions on chlamydial infection in mice and cell cultures.
Fb, G., & Jd, G. (1974) · PubMed · Cited by 6
[Effect of adaptation to altitude hypoxia on the nonspecific immunity indices, production of hemagglutinins and development of adjuvant arthritis in rats].
Fz, M., Evseev, V. A., Davydova, T. V., & Lm, G. (1980) · PubMed · Cited by 1

Flagged first, then by citations

2 of the 126 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

Winn, H. R., Rubio, R., Curnish, R. R. & Berne, R. M. Changes in regional cerebral blood flow (rCBF) caused by increase in CSF concentrations of adenosine and 2-chloroadenosine (CHL-ADO). J. Cereb. Blood Flow Metab. 1, S401–S402 (1981).
Richard, D. E., Berra, E. & Pouyssegur, J. Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1α in vascular smooth muscle cells. J. Biol. Chem. 275, 26765–26771 (2000). · DOI

Sorted by citations

Hypoxia and inflammation
Eltzschig, H. K., & Carmeliet, P. (2011) · New England Journal of Medicine · doi:10.1056/nejmra0910283 · Cited by 2,061
HIF transcription factors, inflammation, and immunity
Palazon, A., Goldrath, A. W., Nizet, V., & Johnson, R. S. (2014) · Immunity · doi:10.1016/j.immuni.2014.09.008 · Cited by 1,195
The hypoxic tumour microenvironment
Petrova, V., Annicchiarico‐Petruzzelli, M., Melino, G., & Amelio, I. (2018) · Oncogenesis · doi:10.1038/s41389-017-0011-9 · Cited by 1,077
Role of oxidative stress and DNA damage in human carcinogenesis
Kryston, T. B., Georgiev, A. B., Pissis, P., & Georgakilas, A. G. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2010.12.016 · Cited by 952
The Neutrophil
Burn, G. L., Foti, A., Marsman, G., Patel, D. F., & Zychlinsky, A. (2021) · Immunity · doi:10.1016/j.immuni.2021.06.006 · Cited by 752

See all 518

Authors: Sitkovsky, M., & Lukashev, D.
Affiliations: Northeastern University (US)
Corresponding author: Sitkovsky, Michail
ORCID: Sitkovsky, Michail
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2005-08-19
Volume: 5
Issue: 9
Pages: 712-721
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri1685
OpenAlex: W2089916504
Semantic Scholar: 86ac33e3809727856e079e987663bd86cf83fd9d
Cited by: 518
References: 126
Citations by year: 2026: 7 · 2025: 16 · 2024: 17 · 2023: 15 · 2022: 14 · 2021: 37 · 2020: 29 · 2019: 18 · 2018: 23 · 2017: 23 · 2016: 21 · 2015: 17 · 2014: 32 · 2013: 38 · 2012: 41
FWCI: 2.31
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: hypoxia, tissue oxygen tension, HIF-1α, adenosine receptors, T cell metabolism, glycolysis, inflammation, innate immune cells, immune cell regulation, energy metabolism
MeSH terms: Animals, T-Lymphocytes, Helper-Inducer, Humans, Oxygen, Partial Pressure, Transcription Factors, Receptors, Purinergic P1, Hypoxia-Inducible Factor 1, alpha Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks