PMID: 9531319Apr 8, 1998Paper

Regulation of macrophage phagocytosis of apoptotic cells by cAMP

The Journal of Immunology : Official Journal of the American Association of Immunologists
A G RossiI Dransfield

Abstract

Regulation of macrophage capacity to remove apoptotic cells may control the balance of apoptotic and necrotic leukocytes at inflamed foci and the extent of leukocyte-mediated tissue damage. Although the molecules involved in the phagocytic process are beginning to be defined, little is known about the underlying regulatory and signaling mechanisms controlling this process. In this paper, we have investigated the effects of treatment of human monocyte-derived macrophages with PGs and other agents that elevate intracellular cAMP on phagocytosis. PGE2 and PGD2 specifically reduced the proportion of macrophages that phagocytosed apoptotic cells. Similar results were obtained with the membrane-permeable cAMP analogues dibutyryl-cAMP and 8-bromo-cAMP but not with the cGMP analogue dibutyryl-GMP. Consistent with the observation that phagocytosis was inhibited by cAMP elevation, treatment of monocyte-derived macrophages with PGE2 resulted in rapid, transient increase in levels of intracellular cAMP. These effects were not due to nonspecific inhibition of monocyte-derived macrophage phagocytosis given that ingestion of Ig-opsonized erythrocytes was unaffected. Elevation of cAMP induced morphologic alterations indicative of changes in th...Continue Reading

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