Hemorrhage induces a reduction in the capacity of macrophages to mobilize intracellular calcium secondary to formyl-methionyl-leucyl-phenylalanine stimulation: Association with alterations in cell surface Fc receptor expression and increased prostaglandin release

Academic Article

Abstract

  • Studies indicate that simple hemorrhage induces profound suppression in splenic and peritoneal macrophage (Mɸ) 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 Mɸ’s ability to mobilize [Ca2+]i. Mɸs 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 Mɸs 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 Mɸs 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 Mɸs to mobilize [Ca2+]i in association with a loss of Fc receptor-positive cells, it appears that the residual Fc receptor-positive Mɸ may be responsible for the enhanced PGE2 productive capacity seen following hemorrhage and may thereby contribute to the induction of the observed host immunosuppression. © 1994 The Shock Society.
  • Authors

    Published In

  • Shock  Journal
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    Author List

  • Ayala A; Chaudry IH
  • Start Page

  • 228
  • End Page

  • 235
  • Volume

  • 1
  • Issue

  • 3