Increase in Phagocytosis after Geldanamycin Treatment or Heat Shock: Role of Heat Shock Proteins
Open accessAbstract
The response to injury is activated at the systemic and cellular levels. At the systemic level, phagocytosis plays a key role in controlling infections and clearing necrotic and apoptotic cells. The expression of heat shock proteins (Hsp), which is a well-conserved process, is a major component of cellular response to stress. This study investigated the relationship between Hsps and phagocytosis. An increase in the phagocytosis of opsonized bacteria particles and latex beads was observed upon incubation of murine macrophages with geldanamycin (GA), a specific inhibitor of the Hsp90 family of proteins. The effect of GA on phagocytosis was blocked by coincubation with inhibitors of transcription (actinomycin D) or translation (cycloheximide), suggesting that gene expression was required. Because expression of Hsps has been observed after GA treatment, the effect of heat shock on phagocytosis was investigated. Similar to GA treatment, heat shock resulted in an actinomycin D-sensitive elevation of phagocytosis, which suggests that Hsps are involved. The increase in phagocytosis after GA treatment was not due to increased binding of opsonized particles to their respective receptors on the macrophage surface or to elevated oxidative stress. However, it was correlated with a rapid polymerization of actin in proximity to the plasma membrane. These results suggest that Hsps play a role in the modulation of the phagocytic process, which is part of the stress response.
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HSPs have been shown to modulate inflammatory response and phagocytosis in macrophages, though their mechanism of action remains unknown.
“HSP's have been shown to modulate inflammatory response and phagocytosis in macrophages, though their mechanism of action remains unknown [52,53].”
From Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium (2008) · cites this paper as [53]
Cites
Araki, N., Johnson, M. T., & Swanson, J. A. (1996) · The Journal of cell biology · doi:10.1083/jcb.135.5.1249 · Cited by 949 · see citing works
Sittler, A. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.12.1307 · Cited by 442 · cited 5× · see citing works
“Hsps are expressed after GA treatment because Hsp90 is a negative regulator of HSF-1 (7, 25, 26).”
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Cited by
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Vega, V., Rodriguez-Silva, M., Frey, T., Gehrmann, M., Díaz, J., Steinem, C., Multhoff, G., Arispe, N., & Maio, A. D. (2008) · Journal of Immunology · doi:10.4049/jimmunol.180.6.4299 · Cited by 455 · see citing works
“Treatment of HepG2 cells with geldanamycin (GA), an inhibitor of Hsp90 that triggers the induction of Hsp70 (20, 21), and destabilizes membranes, also resulted in cell surface detection of Hsp70 by cmHsp70.”
BackgroundSelf-citationMembranes: A meeting point for lipids, proteins and therapies
Escribá, P. V., González‐Ros, J. M., Goñi, F. M., Kinnunen, P. K. J., Vigh, L., Sánchez‐Magraner, L., Fernández, A. M., Busquets, X., Horváth, I., & Barceló‐Coblijn, G. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00281.x · Cited by 454 · see citing works
“The possible role of Hsps as enhancers of endocytosis has been speculated to be part of the cellular stress response for rapid remodelling of the plasma membrane [306].”
BackgroundAn Overview of Biomembrane Functions in Plant Responses to High-Temperature Stress
Niu, Y., & Xiang, Y. (2018) · Frontiers in Plant Science · doi:10.3389/fpls.2018.00915 · Cited by 297 · see citing works
Exosomal Hsp70 Induces a Pro-Inflammatory Response to Foreign Particles Including Mycobacteria
Anand, P., Anand, E., Bleck, C., Anes, E., & Griffiths, G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010136 · Cited by 131 · see citing works
“Earlier studies have also provided indirect evidence that the extracellular presence of Hsp70 can induce increase in phagocytosis of opsonized bacteria [27,28].”
Proteomics Fingerprinting of Phagosome Maturation and Evidence for the Role of a Gα during Uptake
Gotthardt, D., Blancheteau, V., Bosserhoff, A., Ruppert, T., Delorenzi, M., & Soldati, T. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600113-mcp200 · Cited by 98 · see citing works
“They also regulate actin polymerization/capping, uncoating of clathrin-coated vesicles, and phagocytosis in macrophages (53).”
BackgroundThe Role of Hyperthermia in the Multidisciplinary Treatment of Malignant Tumors
Cheng, Y., Weng, S., Yu, L., Zhu, N., Yang, M., & Yuan, Y. (2019) · Integrative Cancer Therapies · doi:10.1177/1534735419876345 · Cited by 106 · see citing works
Jung, B., Lee, Y. K., Hong, J., Ghandehari, H., & Yun, C. (2016) · ACS Nano · doi:10.1021/acsnano.6b06530 · Cited by 93 · see citing works
Chen, F., Pandey, D., Chadli, A., Catravas, J., Chen, T., & Fulton, D. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3669 · Cited by 88 · see citing works
“In a macrophage cell line, Vega and De Maio reported that acute exposure to GA did not influence superoxide formation as measured by nitroblue tetrazolium (43).”
Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium
Sillo, A., Bloomfield, G., Balest, A., Balbo, A., Pergolizzi, B., Peracino, B., Skelton, J., Ivens, A., & Bozzaro, S. (2008) · BMC Genomics · doi:10.1186/1471-2164-9-291 · Cited by 69 · see citing works
“HSP's have been shown to modulate inflammatory response and phagocytosis in macrophages, though their mechanism of action remains unknown [52,53].”
Immunogenic Effect of Hyperthermia on Enhancing Radiotherapeutic Efficacy
Lee, S., Son, B., Park, G., Kim, H., Kang, H., Jeon, J., Youn, H., & Youn, B. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092795 · Cited by 70 · see citing works
Plasmonic photothermal therapy increases the tumor mass penetration of HPMA copolymers
Gormley, A. J., Larson, N., Banisadr, A., Robinson, R., Frazier, N., Ray, A., & Ghandehari, H. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.12.007 · Cited by 71 · see citing works
“Recent findings, for example, have shown that hyperthermia can increase the rate of both endo- and phagocytosis which may then potentiate macromolecular uptake and intracellular delivery [16,17].”
BackgroundLamoke, F., Mazzone, V., Persichini, T., Maraschi, A., Harris, M. B., Venema, R. C., Colasanti, M., Gliozzi, M., Muscoli, C., Bartoli, M., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0304-x · Cited by 61 · see citing works
“Several reports have demonstrated enhanced HSP90 expression as part of the cellular response to oxidative stress conditions [52-54].”
BackgroundThe interaction of heat shock proteins with cellular membranes: a historical perspective
Maio, A. D., & Hightower, L. E. (2021) · Cell Stress and Chaperones · doi:10.1007/s12192-021-01228-y · Cited by 53 · see citing works
The role of hyperthermia in the treatment of tumor
Zhu, W., Pan, S., Zhang, J., Xu, J., Zhang, Y., Zhang, Y., Fu, Z., Wang, Y., Xu, Z., & Xu, Z. (2024) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2024.104541 · Cited by 47 · see citing works
Heat shock effect upon dengue virus replication into U937 cells.
Chávez-Salinas, S., Ceballos-Olvera, I., Valle, J. R.-D., Medina, F., & del Ángel, R. D. (2008) · Virus Research · doi:10.1016/j.virusres.2008.08.012 · Cited by 45
Direct treatment versus indirect: Thermo-ablative and mild hyperthermia effects.
Payne, M., Bossmann, S., & Basel, M. T. (2020) · Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1638 · Cited by 44
A new feature of the stress response: increase in endocytosis mediated by Hsp70
Vega, V., Charles, W., & Maio, A. D. (2010) · Cell stress & chaperones (Print) · doi:10.1007/s12192-009-0165-2 · Cited by 42
Self-citationJahan, K., Nie, H.-T., Yin, Z., Zhang, Y., Li, N., & Yan, X.-W. (2022) · Aquaculture · doi:10.1016/j.aquaculture.2022.737999 · Cited by 37 · see citing works
Pini, T., Leahy, T., & de Graaf, S. P. (2018) · Reproduction, Fertility and Development · doi:10.1071/rd17251 · Cited by 31 · see citing works
Singhto, N., Sintiprungrat, K., & Thongboonkerd, V. (2013) · Journal of Proteome Research · doi:10.1021/pr4004097 · Cited by 33 · see citing works
Dores-Silva, P. R., Cauvi, D. M., Coto, A. L. S., da Silva, N. S. M., Borges, J. C., & Maio, A. D. (2021) · Cell Stress and Chaperones · doi:10.1007/s12192-021-01210-8 · Cited by 32 · see citing works
“In addition, the interaction of HSP70s with membranes has been associated with the endocytic process (Vega et al. 2010), phagocytosis (Vega and De Maio 2005), and the transport of proteins into endosomes as part of the microautophagy (Sahu et al. 2011).”
BackgroundDebnath, A., Tashker, J. S., Sajid, M., & McKerrow, J. (2007) · International Journal of Parasitology · doi:10.1016/j.ijpara.2007.01.016 · Cited by 27
Carey, R. M., Hariri, B. M., Adappa, N. D., Palmer, J. N., & Lee, R. J. (2022) · Cells · doi:10.3390/cells11091478 · Cited by 25 · see citing works
“It was previously shown that geldanamycin treatment and HSP90 inhibition increase phagocytosis after ~90 min due to transcriptional upregulation of HSP70 [107,108].”
BackgroundVega, V., Alexander, L. C. C., Charles, W., Hwang, J. H., Nizet, V., & Maio, A. D. (2014) · Journal of molecular medicine · doi:10.1007/s00109-014-1201-y · Cited by 18
Self-citationKoutsouveli, V., Manousaki, T., Riesgo, A., Lagnel, J., Kollias, S., Tsigenopoulos, C., Arvanitidis, C., Dounas, C., Magoulas, A., & Dailianis, T. (2020) · Frontiers in Marine Science · doi:10.3389/fmars.2019.00786 · Cited by 17 · see citing works
Richards, E. H., Dani, M., Lu, Y., Butt, T. M., & Weaver, R. (2017) · Journal of insect physiology · doi:10.1016/j.jinsphys.2016.10.013 · Cited by 15
Antarctic seals: Molecular biomarkers as indicators for pollutant exposure, health effects and diet.
Lehnert, K., Weirup, L., Harding, K., Härkönen, T., Karlsson, O., & Teilmann, J. (2017) · Science of the Total Environment · doi:10.1016/j.scitotenv.2017.04.224 · Cited by 14
Carles, M., Wagener, B., Lafargue, M., Roux, J., Iles, K., Liu, D., Rodriguez, C., Anjum, N., Zmijewski, J., Ricci, J., et al. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000235 · Cited by 12
Vega, V., Charles, W., & Alexander, L. C. C. (2011) · Cell stress & chaperones (Print) · doi:10.1007/s12192-011-0268-4 · Cited by 12
Self-citationAcidification enhances peritoneal macrophage phagocytic activity.
Grabowski, J., Vega, V., Talamini, M., & Maio, A. D. (2008) · Journal of Surgical Research · doi:10.1016/j.jss.2008.02.049 · Cited by 10 · see citing works
“Once the particle is internalized, it is sealed into a vesicle called the phagosome that is targeted to the lysosome for degradation [10].”
BackgroundMethodInfluentialSelf-citationHeat shock proteins at the crossroads of endosomal trafficking pathways
Zuppini, F., Renzullo, L., Tornatore, F., Poggio, P., & Brancaccio, M. (2025) · Cell Biology and Toxicology · doi:10.1007/s10565-025-10101-y · Cited by 6 · see citing works
“For instance, transferrin internalization is enhanced after heat shock (Vega et al. 2010; López-Hernández et al. 2020) and exposure to heat stress can enhance phagocytic activity in immune cells (Vega and De Maio 2005).”
Mitra, A., Bhakta, K., Kar, A., Roy, A., Mohid, S. A., Ghosh, A., & Ghosh, A. S. (2023) · Molecular Plant Pathology · doi:10.1111/mpp.13350 · Cited by 7 · see citing works
Heat Shock Proteins (Chaperones) and Role in Aquatic Animal Disease Management
Yang, H., Zhang, Y.-Y., & Wei, W.-Z. (2021) · Biotechnological Advances in Aquaculture Health Management · doi:10.1007/978-981-16-5195-3_17 · Cited by 6
In Vitro Evaluation of Colloidal Silver on Immune Function
Franco-Molina, M., Mendoza-Gamboa, E., Zárate-Triviño, D., Coronado-Cerda, E., Alcocer-González, J. M., Reséndez-Pérez, D., Rodríguez-Salazar, M. C., Rivera-Morales, L., Tamez-Guerra, R., & Rodríguez-Padilla, C. (2016) · doi:10.1155/2016/4176212 · Cited by 4
“It is necessary to know the mechanism of selectivity between PBMC and myeloid and lymphoid origin cancer cells and future studies should be developed in the area of receptor-mediated apoptosis such as discussed by “Vega and De Maio, 2005 [14].”
BackgroundKuo, Y.-Y., Lin, G.-B., Chen, W.-T., Chen, Y.-M., Liu, H.-H., & Chao, C. (2024) · bioRxiv · doi:10.1101/2022.12.20.521318 · Cited by 2
“Moreover, heat can up-regulate immune function, such 75 as the phagocytic potential of macrophages and dendritic cells [20, 21], while 76 boosting adaptive immune response [19].”
BackgroundMacrophages and the Stress Response
Vega, V., & Maio, A. D. (2007) · doi:10.1007/978-1-4020-5585-0_5 · Cited by 1
Self-citationMulthoff, G., & Maio, A. D. (2006) · Cell stress & chaperones (Print) · doi:10.1379/csc-203.1 · Cited by 1 · see citing works
Carey, R., Hariri, B. M., Adappa, N., Palmer, J., & Lee, R. J. (2021) · bioRxiv · doi:10.1101/2021.11.16.468387
Impacts of climatic changes on agronomically and physiological processes in plants: A review
Seeda, A., el-Nour, A., & Zaghloul, S. M. (2022) · Middle East Journal of Agriculture Research · doi:10.36632/mejar/2022.11.1.17
Enhanced delivery of polymer therapeutics to solid tumors
Gormley, A., Larson, N., & Ghandehari, H. (2013) · ACS symposium series · doi:10.1021/bk-2013-1135.ch010
- Authors
- Vega, V. L., & De Maio, A.
- Affiliations
- Johns Hopkins University (US)
- Division of Pediatric Surgery, Johns Hopkins University School of Medicine , Baltimore, MD 21205
- ORCID
- Vega, Virginia L
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-10
- Volume
- 175
- Issue
- 8
- Pages
- 5280-5287
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1584354252
- Cited by
- 41
- References
- 54
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM50878, R01GM050878)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- phagocytosis, heat shock proteins, geldanamycin, HSP90 inhibition, heat shock, macrophages, actin polymerization, latex beads, stress response, actinomycin D, cycloheximide, gene expression
- MeSH terms
- Actins, Animals, Cell Line, Gene Expression Regulation, Hot Temperature, Heat-Shock Proteins, Immunoglobulin G, Macrophages, Microspheres, Phagocytosis, Quinones, Benzoquinones, Oxidative Stress, Lactams, Macrocyclic, Mice
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