Heat shock (HS) proteins (HSPs) induce protection against a number of stresses distinct from HS, including reactive oxygen species. In the human premonocytic line U937, we investigated in whole cells the effects of preexposure to HS and exposure to hydrogen peroxide (H202) on mitochondrial membrane potential, mass, and ultrastructure. HS prevented H202-induced alterations in mitochondrial membrane potential and cristae formation while increasing expression of HSPs and the protein product of bcl-2. Protection correlated best with the expression of the 70-kDa HSP, hsp7O. We propose that mitochondria represent a selective target for HS-mediated protection against oxidative injury.

Dendritic cells play a key role in immune responses. There is growing evidence that reactive oxygen species participate in signaling pathways involving nuclear factor (NF)-kappaB, leading to expression of important immune system genes. We found that, unlike H2O2, reactive oxygen species generated by the reaction of oxidase on xanthine induced early phenotypic maturation of dendritic cells by upregulating specific markers CD80, CD83, and CD86 and downregulating mannose receptor-mediated endocytosis. Maturation induced by xanthine oxidase was prevented by allopurinol, an inhibitor of xanthine oxidase activity, and by N-acetylcysteine. The proteasome inhibitor MG-132, which blocks NF-kappaB activation, also inhibited CD86 upregulation, but not endocytosis downregulation by reactive oxygen species. Finally, xanthine-xanthine oxidase enhanced or blocked antigen presentation by dendritic cells depending on whether they had been prepulsed or not with the antigen. Taken together, these results demonstrate that oxidative stress induces phenotypic and functional maturation of dendritic cells, partly through an NF-kappaB-dependent mechanism.

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Proglucagon is processed differentially in pancreatic Finally, GLP-1-(1-37) was cleaved to tGLP-1 in vitro by purified recombinant PC3. Taken together, these results indicate that PC3 has the same specificity as the convertase that is responsible for the processing of proglucagon to tGLP-1, glicentin and oxyntomodulin in the intestinal L cell, and it is concluded that this enzyme is thus able to act alone in this processing pathway.

Induction of specific heat shock (HS) proteins (HSP) has been described as a response of human monocytes to phagocytosis, and HSP may play protective roles in infection and immunity. Here we compared the stress response in monocytes and polymorphonuclear neutrophils during exposure to the classical inducers of HSP, i.e., HS and cadmium. We also investigated the stress response in these two phagocytic cells after particulate (phagocytosis) and nonparticulate [f-Met-Leu-Phe (FMLP)] activation of the respiratory burst enzyme NADPH oxidase. HS and cadmium induced stress protein synthesis in both cell types. In contrast, phagocytosis induced HSP in monocytes only, while FMLP did so in neutrophils only. This differential regulation of stress proteins might relate to physiological and functional differences between monocytes and neutrophils. With respect to functional effects of HS, we examined, in human monocytes and in neutrophils, the effect of HS on NADPH oxidase-mediated O2- generation as well as on phagocytosis, bacterial killing, and superoxide dismutase (SOD) activity. In monocytes, as in neutrophils, NADPH oxidase activity was inhibited by HS, while thermotolerance prevented this inhibition. Phagocytosis and bacterial killing were unaltered by HS. SOD activity transiently increased in monocytes but decreased in neutrophils upon exposure to HS. These observations indicate differential induction of HSP in human phagocytes and differential regulation of phagocytes' functions by HS.

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