Abstract
Inflammation results from the recruitement to a given tissue or organ and the activation of leucocytes, among which the monocytes-macrophages play a major role. These phagocytic cells produce high levels of reactive oxygen species (ROS) as well as cytokines. Whereas both ROS and cytokines have the potential to regulate the expression of heat shock (HS)/stress proteins (HSP), it appears that these proteins in turn have the ability to protect cells and tissues from the deleterious effects of inflammation. The mechanisms by which such protection occurs include prevention of ROS-induced DNA strand breaks and lipid peroxidation as well as protection from mitochondrial structure and function. In vivo, HS protects organs against a number of lesions associated with the increased production of ROS and/or cytokines. In an animal model for adult respiratory distress syndrome, an acute pulmonary inflammatory condition, HS completely prevented mortality. HSP (hsp70 in particular) may also exert protective effects in the immune system by contributing to the processing and presentation of bacterial and tumoral antigens. The analysis of the expression of hsp70 may prove of diagnostic and prognostic value in inflammatory conditions and therapeutical applications are being considered.
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References
Babior, B. M., The respiratory burst oxidase. Trends biochem. Sci.12 (1987) 241–243.
Barrios, C., Lussow, A. R., Embden, J. V., Van der Zee, R., Rappuoli, R., Costantino, P., Louis, J. A., Lambert, P., and Del Giudice, G., Mycobacterial heat-shock proteins as carrier molecules. II The use of the 70k-Da mycobacterial heat-shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and Bacillus Calmette-Guérin priming. Eur. J. Immun.22 (1992) 1365–1372.
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., and Freman, B. A., Apparent hydroxyl radical production by peroxinitrite: implication for endothelial injury from nitric oxide and superoxide. Proc. natl Acad. Sci. USA87 (1990) 1620–1624.
Birnobim, H. C., and Jevcak, J. J., Fluorimetric method for rapid detection of DNA strand breaks in human white blood cells produced by low doses of radiation. Cancer Res.41 (1988) 1889–1892.
Buchmeier, N. A., and Heffron, F., Induction of Salmonella stress proteins upon infection of macrophages. Science248 (1990) 730–733.
Christman, M. F., Morgan, R. W., Jacobson, F. S., and Ames, B., Control of a regulation for defenses against oxidative stress and some heat shock proteins in Salmonella typhimurium. Cell41 (1985) 753–762.
Clark, R. A., The human neutrophil respiratory burst oxidase. J. infect. Dis.,161 (1990) 1140–1147.
Cohen, M. S., Phagocytes in health and disease. Curr. Opinion infect. Dis.4 (1991) 338–343.
Corbett, J. A., Lancaster, J. R., Sweetland, M. A., and McDaniel, M. L., Interleukin-1 β-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. J. biol. Chem.266 (1991) 21351–21354.
Cossarizza, A., Baccarani-Contri, M., Kalashnikova, G., and Franceschi, C., A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetraethylbenzimidazolcarbocyanine iodine (JC-1). Biochem. biophys. Res. Commun.197 (1993) 40–45.
DeNagel, D. C., and Pierce, S. K., Heat shock proteins in immune responses. Critical. Rev. Immun.13 (1993) 71–81.
Fincato, G., Polentarutti, N., Sica, A., Mantovani, A., and Colotta, F., Expression of a heat-inducible gene of the HSP70 family in human myelomonocytic cells: regulation by bacterial products and cytokines. Blood77 (1991) 579–586.
Fuller, K. J., Issels, R. D., Slosman, D. O., Guillet, J.-G., Soussi, T., and Polla, B. S., Cancer and the heat shock response. Eur. J. of Cancer (1994) in press.
Gardner, H. W., Oxygen radical chemistry of polyunsaturated fatty acids. Free Rad. Biol. Med.7 (1989) 65–86.
Hainaut, P., and Milner, J., Interaction of heat-shock protein 70 with p53 translated in vitro: evidence for interaction with dimeric p53 and for a role in the regulation of p53 conformation. EMBO J.11 (1992) 3513–3520.
Helqvist, S., Polla, B. S., Johannesen, J., and Nerup, J., Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1 β. Diabetologia34 (1991) 150–156.
Henry, Y., Lepoivre, M., Drapier, J. C., Ducrocq, C., Boucher, J. L., and Guissani, A., EPR characterization of molecular targets for NO in mammalian cells and organelles. FASEB J.7 (1993) 1124–1134.
Hollstein, M., Sidransky, D., Vogelstein, B., and Harris, G. G., p53 mutations in human cancer. Science253 (1991) 49–53.
Jäättelä, M., Saksela, K., and Saskela, K., Heat shock protects WEHI-164 target cells from the cytolysis by tumor necrosis α and β. Eur. J. Immun.19 (1989) 1413–1417.
Jäättelä, M., Wissing, D., Bauer, P. A., and Li, G. C., Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity. EMBO J.11 (1992) 3507–3512.
Jäättelä, M., and Wissing, D., Heat-shock proteins protect cells from monocytes cytotoxicity: possible mechanism of self-protection. J. expl. Med.177 (1993) 231–236.
Jäättelä, M., Overexpression of major heat shock protein hsp70 inhibits tumor necrosis factor-induced activation of phospholipase A2. J. Immun.151 (1993) 4286–4294.
Jolliet, P., Slosman, D. O., and Polla B. S., Heat shock proteins in critical illness: markers of cellular stress or more? In: Yearbook of Intensive Care and Emergency Medicine, pp. 24–34. Ed. J.-L. Vincent. Springer Verlag, Berlin-Heidelberg-New York 1994.
Kantengwa, S., Capponi, A. M., Beventre, J. V., and Polla, B. S., Calcium and the heat shock protein response in the human monocytic line U-937. Am. J. Physiol.259 (1990) C77-C83.
Kantengwa, S., Donati, Y. R. A., Clerget, M., Maridonneau-Parini, I., Sinclair, F., Mariéthoz, E., Perin M., Rees, A. D. M., Slosman, D. O., and Polla, B. S., Heat shock proteins: an autoprotective mechanism for inflammatory cells? Semin. Immun.3 (1991) 49–56.
Kindås-Mügge, I., Hammerle, A. H., Fröhlich, I., Oismüller, C., Micksche, M., and Trauringer, F., Granulocytes of critically ill patients spontaneously express the 72 kD heat shock protein. Circulatory Shock39 (1993) 247–252.
Lukic, M. L., Stosic-Grujicic, S., Ostojic, N., Chan, W. L., and Liew, F. Y., Inhibition of nitric oxide generation affects the induction of diabetes by streptozotocin in mice. Biochem. biophys. Res. Commun.178 (1991) 913–920.
Maridonneau-Parini, I., Malawista, S. E., Stubbe, H., Russo-Marie, F., and Polla, B. S., Heat shock in human neutrophilis: superoxide generation is inhibited by a mechanism distinct from heat-denaturation of NADPH oxidase and is protected by heat shock proteins in thermotolerant cells. J. Cell Physiol.156 (1993) 204–211.
Margulis, B. A., Sandler, S., Eizirik, D. L., Welsh, N., and Welsh M., Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1β-induced impaired β-cell function. Diabetes40 (1991) 1418–1422.
Mariéthoz, E., Tacchini-Cottier, F., Jacquier-Sarlin, M. R., Sinclair, F., and Polla B. S., Exposure of monocytes to heat shock does not increase class II expression but modulates antigen-dependent T cell responses. Int. Immun.6 (1994) 925–930.
Minota, S., Cameron, B., Welch, W. J., and Winfield, J. B., Auto-antibodies to the constitutive 73-kD member of the hsp70 family of the heat shock proteins in systemic lupus erythematosus. J. expl Med.168 (1988) 1475–1480.
Moncada, S., and Higgs, E. A., The L-arginine-nitric oxide pathway. N. Engl. J. Med.329 (1993) 3051–3064.
Mosser, D. D., and Martin, L. H., Induced thermotolerance to apoptosis in a human T lymphocyte cell line. J. Cell. Physiol.151 (1992) 561–570.
Nathan, C. F., and Hibbs, J. B. Jr, Role of nitric oxide synthesis in macrophages antimicrobial activity. Curr. Opinion Immun.3 (1991) 65–70.
Perin Minisini, M., Kantengwa, S., and Polla, B. S., DNA damage and stress protein synthesis induced by oxidative stress proceed independently in the human premonocytic line U937. Mutat. Res. DNA Repair315 (1994) 169–179.
Perin Minisini, Richard, M.-J. and Polla, B. S., Radicaux libres de l'oxygéne: role pathogénique et cibles thérapeutiques dans l'athérosclérose. STV6 (1994) 321–329.
Petros, A., Bennett, D., and Vallance, P., Effect of nitric oxide synthetase on hypotension in patients with septic shock. Lancet338 (1991) 1557–1558.
Pinhasi-Kimhi, O., Michalovitz, D., Ben-Ze'ev A., and Oren, M., Specific interaction between the p53 cellular tumor antigen and major heat shock proteins. Nature320 (1986) 182–185.
Polla, B. S., and Bonventre, J. V., Heat shock protects cells dependent on oxidative metabolism from inhibition of oxidative phosphorylation. Clin. Res.35 (1987) 555A.
Polla, B. S., Pittet, N., and Slosman, D. O., Heat shock (HS) protects the human monocytic line U937 from bleomycin (BLM)-mediated oxidative injury. Eur. Respir. J.3 Suppl. (1990) 335S, 1355A.
Polla, B. S., Bonventre, J. V., and Krane, S. M. 1, 25-Dihydroxyvitamin D3 increases the toxicity of hydrogen peroxide in human monocytic U-937: The role of calcium and heat shock. J. Cell Biol.107 (1988) 373–380.
Polla, B. S., Kantengwa, S., Gleich, G. J., Kondo, M., Reimert, C. M., and Junod, A. F., Spontaneous heat shock protein synthesis by alveolar macrophages in interstitial lung disease associated with phagocytosis of eosinophils. Eur. resp. J.6 (1993) 483–488.
Richard M.-J., Guiraud, P., Meo, J., and Favier, A., High performance liquid chromatographic separation of malondialdehyde-thiobarbituric acid adduct in biological materials (plasma and human cells) using a commercially available reagent. J. Chromat.577 (1992) 9–18.
Richter, D., and Harn, D. A., Candidate vaccine antigens identified by antibodies from mice vaccinated with 15- or 50-kilorad-irradiated cercariae ofShistosoma mansoni. Infect. Immun.61 (1993) 146–154.
Richter, D., Incani, R. N., and Harn, D. A., Isotype response to candidate vaccine antigens in protective sera obtained from mice vaccinated with irradiated cercariae ofShistosoma mansoni. Infect. Immun.61 (1993) 3003–3011.
Sellins, K. S., and Cohen, J., Hyperthermia induces apoptosis in thymocytes. Radiat. Res.126 (1991) 88–95.
Smejkal, R. M., Wolff, R., and Olenick, J. G.,Leismania braziliensis panamensis: increased infectivity resulting from heat shock. Expl Parasit.65 (1988) 1–9.
Van Buskirk, A., Crump, B. L., Margoliash, E., and Pierce, S. K., A peptide binding proteins having a role in antigen presentation is a member of the HSP70 heat shock family. J. expl Med.170 (1989) 1799–1803.
Villar, J., Edelson, J. D., Post, M., Mullen B. M., and Slutzky, A. S., Induction of heat stress proteins is associated with decreased mortality in an animal model of acute lung injury. Am. Rev. resp. Dis.147 (1993) 177–181.
Young, D., Lathigra, R., Hendirx, R., Sweetser, D., and Young, R. A., Stress proteins are immune targets in leprosy and tuberculosis. Proc. natl Acad. Sci. USA85 (1988) 4267–4270.
Zarley, J. H., Britigan, B. E., and Wilson, M. E., Hydrogen peroxide-mediated toxicity for Leishmania donovani chagasi promastigotes. Role of hydroxyl radical and protection by heat shock. J. clin. Invest.88 (1991) 1511–1521.
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Jacquier-Sarlin, M.R., Fuller, K., Dinh-Xuan, A.T. et al. Protective effects of hsp70 in inflammation. Experientia 50, 1031–1038 (1994). https://doi.org/10.1007/BF01923458
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DOI: https://doi.org/10.1007/BF01923458