CoChat
Sign Up
Cited by 34Phagocytosis and Immune RegulationCell Adhesion Molecules ResearchAdipokines, Inflammation, and Metabolic Diseases

Signal Regulatory Protein α Negatively Regulates β2 Integrin-Mediated Monocyte Adhesion, Transendothelial Migration and Phagocytosis

Open access
Liu, Dan-Qing, Li, Li-Min, Guo, Ya-Lan, Bai, Rui, Wang, Chen, Bian, Zhen, Zhang, Chen-Yu, Zen, Ke·2008·PLoS ONE
DOI 10.1371/journal.pone.0003291PMC PMC2553263
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Signal regulate protein alpha (SIRPalpha) is involved in many functional aspects of monocytes. Here we investigate the role of SIRPalpha in regulating beta(2) integrin-mediated monocyte adhesion, transendothelial migration (TEM) and phagocytosis. METHODOLOGY/PRINCIPAL FINDINGS: THP-1 monocytes/macropahges treated with advanced glycation end products (AGEs) resulted in a decrease of SIRPalpha expression but an increase of beta(2) integrin cell surface expression and beta(2) integrin-mediated adhesion to tumor necrosis factor-alpha (TNFalpha)-stimulated human microvascular endothelial cell (HMEC-1) monolayers. In contrast, SIRPalpha overexpression in THP-1 cells showed a significant less monocyte chemotactic protein-1 (MCP-1)-triggered cell surface expression of beta(2) integrins, in particular CD11b/CD18. SIRPalpha overexpression reduced beta(2) integrin-mediated firm adhesion of THP-1 cells to either TNFalpha-stimulated HMEC-1 monolayers or to immobilized intercellular adhesion molecule-1 (ICAM-1). SIRPalpha overexpression also reduced MCP-1-initiated migration of THP-1 cells across TNFalpha-stimulated HMEC-1 monolayers. Furthermore, beta(2) integrin-mediated THP-1 cell spreading and actin polymerization in response to MCP-1, and phagocytosis of bacteria were both inhibited by SIRPalpha overexpression. CONCLUSIONS/SIGNIFICANCE: SIRPalpha negatively regulates beta(2) integrin-mediated monocyte adhesion, transendothelial migration and phagocytosis, thus may serve as a critical molecule in preventing excessive activation and accumulation of monocytes in the arterial wall during early stage of atherosclerosis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0003291

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • SIRPα inhibits phagocytosis.

    “a factor shown previously to inhibit phagocytosis [211]”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [211]

  • LPS induces expression of miR-17, miR-20a, and miR-106a, which collectively target SIRPα.

    “Zhu et al. reported that LPS induces expression of miR-17, miR-20a, and miR-106a, which collectively target signal regulatory protein alpha (SIRPα)”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [211]

    The Results and Discussion describe how changing SIRPα levels affects β2-integrin-mediated responses, but do not address the claimed microRNAs. Searches for miR-17, miR-20a, miR-106a, and LPS found no passage saying that LPS induces these microRNAs or that they target SIRPα; the References list an LPS-related study without making that claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 46

  1. [1]Gerrity RG 1981 The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol 103 181 190 7234961 PMC1903817
  2. [2]Ross R 1993 The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362 801 809 8479518
  3. [3]Rosenfeld ME 2002 Leukocyte recruitment into developing atherosclerotic lesions: the complex interaction between multiple molecules keeps getting more complex. Arterioscler Thromb Vasc Biol 22 361 363 11884275
  4. [4]Boisvert WA Santiago R Curtiss LK Terkeltaub RA 1998 A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 101 353 363 9435307 PMC508574
  5. [5]Dong ZM Chapman SM Brown AA Frenette PS Hynes RO 1998 The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 102 145 152 9649568 PMC509076
  6. [6]Springer TA 1994 Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76 301 314 7507411
  7. [7]Campbell JJ Hedrick J Zlotnik A Siani MA Thompson DA 1998 Chemokines and the arrest of lymphocytes rolling under flow conditions. Science 279 381 384 9430588
  8. [8]Han KH Chen Y Chang MK Han YC Park JH 2003 LDL activates signaling pathways leading to an increase in cytosolic free calcium and stimulation of CD11b expression in monocytes. J Lipid Res 44 1332 1340 12730301
  9. [9]Oshima K Ruhul Amin AR Suzuki A Hamaguchi M Matsuda S 2002 SHPS-1, a multifunctional transmembrane glycoprotein. FEBS Lett 519 1 7 12023008
  10. [10]Jiang P Lagenaur CF Narayanan V 1999 Integrin-associated protein is a ligand for the P84 neural adhesion molecule. Journal of Biological Chemistry 274 559 562 9872987
  11. [11]Timms JF Carlberg K Gu H Chen H Kamatkar S 1998 Identification of major binding proteins and substrates for the SH2-containing protein tyrosine phosphatase SHP-1 in macrophages. Mol Cell Biol 18 3838 3850 9632768 PMC108968
  12. [12]Saginario C Sterling H Beckers C Kobayashi R Solimena M 1998 MFR, a putative receptor mediating the fusion of macrophages. Mol Cell Biol 18 6213 6223 9774638 PMC109208
  13. [13]Patel V Smith RE Serra A Brooke G Howard CJ 2002 MyD-1 (SIRPalpha) regulates T cell function in the absence of exogenous danger signals, via a TNFalpha-dependent pathway. Eur J Immunol 32 1865 1872 12115605
  14. [14]Barclay AN Brown MH 2006 The SIRP family of receptors and immune regulation. Nat Rev Immunol 6 457 464 16691243
  15. [15]Liu Y Soto I Tong Q Chin A Buhring HJ 2005 SIRPbeta1 is expressed as a disulfide-linked homodimer in leukocytes and positively regulates neutrophil transepithelial migration. J Biol Chem 280 36132 36140 16081415
  16. [16]Fujioka Y Matozaki T Noguchi T Iwamatsu A Yamao T 1996 A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. Mol Cell Biol 16 6887 6899 8943344 PMC231692
  17. [17]Kharitonenkov A Chen Z Sures I Wang H Schilling J 1997 A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature 386 181 186 9062191
  18. [18]Yamao T Noguchi T Takeuchi O Nishiyama U Morita H 2002 Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1. J Biol Chem 277 39833 39839 12167615
  19. [19]Okazawa H Motegi S Ohyama N Ohnishi H Tomizawa T 2005 Negative regulation of phagocytosis in macrophages by the CD47-SHPS-1 system. J Immunol 174 2004 2011 15699129
  20. [20]Smith RE Patel V Seatter SD Deehan MR Brown MH 2003 A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes. Blood 102 2532 2540 12805067
  21. [21]Liu Y Buhring HJ Zen K Burst SL Schnell FJ 2002 Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration. J Biol Chem 277 10028 10036 11792697
  22. [22]de Vries HE Hendriks JJ Honing H De Lavalette CR van der Pol SM 2002 Signal-regulatory protein alpha-CD47 interactions are required for the transmigration of monocytes across cerebral endothelium. J Immunol 168 5832 5839 12023387
  23. [23]Liu SQ Alkema PK Tieche C Tefft BJ Liu DZ 2005 Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein alpha and Src homology 2 domain-containing protein-tyrosine phosphatase-1. J Biol Chem 280 39294 39301 16159885
  24. [24]Inagaki K Yamao T Noguchi T Matozaki T Fukunaga K 2000 SHPS-1 regulates integrin-mediated cytoskeletal reorganization and cell motility. Embo J 19 6721 6731 11118207 PMC305898
  25. [25]Wu CJ Chen Z Ullrich A Greene MI O'Rourke DM 2000 Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and glioblastoma phenotype by signal-regulatory proteins (SIRPs). Oncogene 19 3999 4010 10962556
  26. [26]Valcourt U Merle B Gineyts E Viguet-Carrin S Delmas PD 2007 Non-enzymatic glycation of bone collagen modifies osteoclastic activity and differentiation. J Biol Chem 282 5691 5703 17142454
  27. [27]Zen K Liu Y Cairo D Parkos CA 2002 CD11b/CD18-dependent interactions of neutrophils with intestinal epithelium are mediated by fucosylated proteoglycans. J Immunol 169 5270 5278 12391246
  28. [28]Ades EW Candal FJ Swerlick RA George VG Summers S 1992 HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol 99 683 690 1361507
  29. [29]Zen K Cui LB Zhang CY Liu Y 2007 Critical Role of Mac-1 Sialyl Lewis X Moieties in Regulating Neutrophil Degranulation and Transmigration. J Mol Biol 17919658
  30. [30]Ryu JW Hong KH Maeng JH Kim JB Ko J 2004 Overexpression of uncoupling protein 2 in THP1 monocytes inhibits beta2 integrin-mediated firm adhesion and transendothelial migration. Arterioscler Thromb Vasc Biol 24 864 870 15016641
  31. [31]Luscinskas FW Ding H Tan P Cumming D Tedder TF 1996 L- and P-selectins, but not CD49d (VLA-4) integrins, mediate monocyte initial attachment to TNF-alpha-activated vascular endothelium under flow in vitro. J Immunol 157 326 335 8683134
  32. [32]Zhang H Issekutz AC 2002 Down-modulation of monocyte transendothelial migration and endothelial adhesion molecule expression by fibroblast growth factor: reversal by the anti-angiogenic agent SU6668. Am J Pathol 160 2219 2230 12057924 PMC1850845
  33. [34]Miyata T Inagi R Iida Y Sato M Yamada N 1994 Involvement of beta 2-microglobulin modified with advanced glycation end products in the pathogenesis of hemodialysis-associated amyloidosis. Induction of human monocyte chemotaxis and macrophage secretion of tumor necrosis factor-alpha and interleukin-1. J Clin Invest 93 521 528 8113390 PMC293873
  34. [37]Simon DI Chen Z Xu H Li CQ Dong J 2000 Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 192 193 204 10899906 PMC2193258
  35. [38]Sotiriou SN Orlova VV Al-Fakhri N Ihanus E Economopoulou M 2006 Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. Faseb J 20 559 561 16403785
  36. [39]Mateo V Brown EJ Biron G Rubio M Fischer A 2002 Mechanisms of CD47-induced caspase-independent cell death in normal and leukemic cells: link between phosphatidylserine exposure and cytoskeleton organization. Blood 100 2882 2890 12351399
  37. [40]Gafa V Manches O Pastor A Drouet E Ambroise-Thomas P 2005 Human cytomegalovirus downregulates complement receptors (CR3, CR4) and decreases phagocytosis by macrophages. J Med Virol 76 361 366 15902695
  38. [41]Shi C Zhang X Chen Z Sulaiman K Feinberg MW 2004 Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1. J Clin Invest 114 408 418 15286807 PMC484980
  39. [42]Capo C Moynault A Collette Y Olive D Brown EJ 2003 Coxiella burnetii avoids macrophage phagocytosis by interfering with spatial distribution of complement receptor 3. J Immunol 170 4217 4225 12682255
  40. [43]Kong XN Yan HX Chen L Dong LW Yang W 2007 LPS-induced down-regulation of signal regulatory protein {alpha} contributes to innate immune activation in macrophages. J Exp Med 204 2719 2731 17954568 PMC2118489
  41. [44]Shahabuddin S Ponath P Schleimer RP 2000 Migration of eosinophils across endothelial cell monolayers: interactions among IL-5, endothelial-activating cytokines, and C-C chemokines. J Immunol 164 3847 3854 10725746
  42. [45]Papayannopoulou T Priestley GV Bonig H Nakamoto B 2003 The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization. Blood 101 4739 4747 12595315
  43. [46]Weber KS Klickstein LB Weber C 1999 Specific activation of leukocyte beta2 integrins lymphocyte function-associated antigen-1 and Mac-1 by chemokines mediated by distinct pathways via the alpha subunit cytoplasmic domains. Mol Biol Cell 10 861 873 10198043 PMC25207
  44. [47]Aiello RJ Bourassa PA Lindsey S Weng W Freeman A 2002 Leukotriene B4 receptor antagonism reduces monocytic foam cells in mice. Arterioscler Thromb Vasc Biol 22 443 449 11884288
  45. [48]van Royen N Hoefer I Bottinger M Hua J Grundmann S 2003 Local monocyte chemoattractant protein-1 therapy increases collateral artery formation in apolipoprotein E-deficient mice but induces systemic monocytic CD11b expression, neointimal formation, and plaque progression. Circ Res 92 218 225 12574150
  46. [49]Brown E 2001 Integrin-associated protein (CD47): an unusual activator of G protein signaling. J Clin Invest 107 1499 1500 11413154 PMC200200

Cited by

Sorted by citations

Authors
Liu, D.-Q., Li, L.-M., Guo, Y.-L., Bai, R., Wang, C., Bian, Z., Zhang, C.-Y., & Zen, K.
Affiliations
State Key Laboratory of Pharmaceutical Biotechnology (CN)
Corresponding author
Zen, Ke
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2008-09-29
Volume
3
Issue
9
Pages
e3291
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0003291
PMC
PMC2553263
OpenAlex
W2056412907
Cited by
34
References
3
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 4
FWCI
0.98
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Georgia State University
  • Centers for Disease Control and Prevention
  • National Key Research and Development Program of China
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
SIRPα, beta2 integrins, monocyte adhesion, transendothelial migration, phagocytosis, advanced glycation end products, MCP-1, CD11b/CD18, ICAM-1, actin polymerization, atherosclerosis, THP-1 cells, monocyte chemotaxis
MeSH terms
Antigens, Differentiation, Cell Adhesion, Cell Line, Cell Movement, Humans, Models, Biological, Monocytes, Phagocytosis, Receptors, Immunologic, Recombinant Proteins, Down-Regulation, CD18 Antigens, Chemokine CCL2, CD11b Antigen, Atherosclerosis

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