Contribution of heat shock proteins to cell protection from complement-mediated lysis.
The possible participation of hsc70 and hsp70 in cellular protection from complement damage was studied. Human erythroleukemia K562 cells were pretreated with reagents affecting hsc70 or hsp70, and cell sensitivity to lysis by antibody and human complement was examined. Treatment with deoxyspergualin, an hsc70 inhibitor, sensitized K562 cells to complement lysis, whereas treatment with ethanol, butanol or hemin, inducers of hsc70 synthesis, protected the cells from complement-mediated lysis. Incubation of K562 at either 42 degrees C or with the amino acid analogue L-azetidine-2-carboxylic acid induced synthesis of hsp70, but not of hsc70. The latter treatment also conferred elevated resistance to complement lysis on K562 cells. Pretreatment of K562 cells with sub-lethal doses of complement desensitizes them to lethal complement doses. No effect of sublytic complement on synthesis of hsc70 and hsp70 was found. However, the results demonstrated that complement stress causes translocation of hsc70 from the cytoplasm to the K562 cell surface. Two monoclonal and two polyclonal antibodies identified hsc70 on the surface of intact, viable complement-stressed cells, while antibodies directed to hsp70 did not bind to these cells. Altogether, the results suggest that the heat shock proteins hsc70 and hsp70 play a role in cell defense against complement.
Fishelson
Z
Z
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Hochman
I
I
Greene
L E
LE
Eisenberg
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E
D000438:Alcohols / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D001384:Azetidines / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020014:K562 Cells; D014407:Tumor Cells, Cultured
D000438:Alcohols; D001384:Azetidines; D006146:Guanidines; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D007166:Immunosuppressive Agents; C082735:azetidine; D006427:Hemin; D003165:Complement System Proteins; C037258:gusperimus