HEMORRHAGE INDUCES A REDUCTION IN THE CAPACITY OF MACROPHAGES TO MOBILIZE INTRACELLULAR CALCIUM SECONDARY TO FORMYL-METHIONYL-LEUCYL-PHENYLALANINE STIMULATION

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Abstract
Studies indicate that simple hemorrhage induces profound suppression in splenic and peritoneal macrophage (MØ;) functions such as antigen presentation, reduced major histocompatibility complex class II antigen expression, as well as cytokine release. Since many of these macrophage functions require the mobilization of [Ca2+]i, our aim was to determine whether or not hemorrhage produced changes in the splenic and/or peritoneal MØ ability to mobilize [Ca2+]i. MØs taken from mice (C3H/HeN) 2 h posthemorrhage (1 h duration; 35 mm Hg), exhibited a significantly reduced capacity to mobilize [Ca2+]i when exposed to formyl-methionyl-leucyl-phenylalanine (FMLP) compared to shams. This loss of the capacity to mobilize [Ca2+]i in response to FMLP stimulation was not due to an inability of MØs to recruit Ca2+ from extracellular sources. Staurosporine pretreatment ablated the response to FMLP and, since these cells produced less inositol 1,4,5-triphosphate, this indicates that MØs taken from hemorrhage animals are unable to recruit Ca2+ from intracellular stores. This dysfunction, which was observed following hemorrhage, was associated with the decrease in the number of Fc receptor-positive cells. However, despite this loss, the residual Fc receptor-positive cells present following hemorrhage were capable of releasing enhanced levels of PGE2. It may well be that the residual Fc receptor population represents a sub-population of cells which have been differentially primed for enhanced PGE2 release by the hypotensive insult. Thus while hemorrhage reduces the capacity of MØs to mobilize [Ca2+] in association with a loss of Fc receptor-positive cells, it appears that the residual Fc receptor-positive MØ may be responsible for the enhanced PGE2 productive capacity seen following hemorrhage and may thereby contribute to the induction of the observed host immunosuppression.

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