Erythrophagocytosis induces heat shock protein synthesis by human monocytes-macrophages.
Exposure of cells to elevated temperatures and other environmental stresses results in the expression of specific genes encoding the so-called heat shock proteins (HSPs). Since exogenous H2O2 induces in human monocytes the synthesis of HSPs, and previous induction of HSPs protects these cells from oxidative injury, we investigated whether HSP synthesis was also induced during generation of reactive oxygen species by the phagocyte itself during phagocytosis. As a model system, we analyzed the effects of erythrophagocytosis on protein synthesis by the human premonocytic line U937, in which phagocytosis is induced during differentiation with 1,25-dihydroxyvitamin D3. Exposure to whole erythrocytes, but not to erythrocyte ghosts, induced in the phagocytic cells only the synthesis of the 70- and 83- to 90-kDa HSPs and a 32-kDa oxidation-related stress protein identical by partial peptide mapping to heme oxygenase. The radioprotective aminothiol N-(2'-mercaptoethyl)-1,3-propanediamine (WR-1065), which can substitute for glutathione as hydrogen donor, prevented this induction. These results suggest that oxygen free radicals generated in the presence of hemoglobin-derived iron and consecutive glutathione depletion are involved in induction of stress protein synthesis during erythrophagocytosis. HSPs synthesized during phagocytosis may play a role in the phagocyte's defense mechanisms and in protective immunity.
Clerget
M
M
Department of Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Polla
B S
BS
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line; D004910:Erythrocyte Membrane / Q000502:physiology; D004912:Erythrocytes / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010449:Peptide Mapping; D010587:Phagocytosis; D012756:Sheep; D013481:Superoxides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D006360:Heat-Shock Proteins; D013481:Superoxides; D015054:Zymosan; D002117:Calcitriol