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J Surg Res. 1994 Jul;57(1):221-6.

Alterations in macrophage signal transduction pathways mediate post-traumatic changes in macrophage function.

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1
Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia 19104.

Abstract

After injury, macrophage effector function diminishes while suppressor function increases. Protein kinase C (PKC), which initiates superoxide synthesis and phagocytosis, and phospholipase A2 (PLA2), which initiates eicosanoid metabolism, are key enzymes in cell signal transduction, which may mediate this change in cell function. The aim of this study was to investigate the effect of trauma on macrophage signal transduction. Swiss-Webster (CFW) mice (n = 210) were randomized to control or hindlimb amputation groups. Animals were sacrificed 24 hr after injury. Peritoneal macrophage function was assessed by measurement of superoxide anion (O2-), Fc, mannose-fucose-mediated phagocytosis, and PGE2 release. Membrane and cytosolic PKC activity were measured by radioimmunoassay in unstimulated and phorbol ester-stimulated cells. Membrane fatty acids and PLA2 activity were measured by thin-layer chromatography. Hindlimb amputation resulted in significantly decreased superoxide anion synthesis (0.7 +/- 0.2 nm vs 1.7 +/- 0.3 nmol/l/10(6) cells in controls, P < 0.01) and phagocytosis and a significant increase in prostaglandin E2 synthesis. This was associated with a shift in cell membrane metabolism with increased PLA2 activity, arachidonic acid turnover, and a significant reduction in PKC membrane translocation in response to phorbol ester. Together these data demonstrate an alteration in signal transduction pathways, which may account for the observed change in macrophage function after injury.

PMID:
8041143
DOI:
10.1006/jsre.1994.1135
[Indexed for MEDLINE]

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