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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Regulation of macrophage phagocytosis of apoptotic cells by cAMP

A G Rossi1, J C McCutcheon, N Roy

  • 1Department of Medicine (RIE), Rayne Laboratory, The University of Edinburgh Medical School, Scotland, UK. a.g.rossi@ed.ac.uk

Journal of Immunology (Baltimore, Md. : 1950)
|April 8, 1998
PubMed

Insights

Prostaglandins E2 and D2, which increase cyclic AMP (cAMP) levels, reduce macrophage phagocytosis of apoptotic cells. This suggests cAMP signaling regulates inflammation resolution and offers a therapeutic target.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Macrophage phagocytosis of apoptotic cells is crucial for resolving inflammation and preventing tissue damage.
  • The regulatory and signaling mechanisms controlling this phagocytic process are not well understood.

Purpose of the Study:

  • To investigate the effects of prostaglandins (PGs) and agents that elevate intracellular cyclic adenosine monophosphate (cAMP) on the phagocytic capacity of human monocyte-derived macrophages.
  • To explore the role of cAMP signaling pathways in regulating macrophage-mediated clearance of apoptotic cells.

Main Methods:

  • Human monocyte-derived macrophages were treated with PGE2, PGD2, cAMP analogues (dibutyryl-cAMP, 8-bromo-cAMP), and a cGMP analogue (dibutyryl-GMP).
  • Phagocytosis of apoptotic cells and Ig-opsonized erythrocytes was assessed.
  • Intracellular cAMP levels and macrophage morphology were analyzed following PGE2 treatment.

Main Results:

  • PGE2 and PGD2 significantly reduced the proportion of macrophages phagocytosing apoptotic cells.
  • Elevating intracellular cAMP with analogues mimicked this inhibitory effect, while cGMP analogues had no impact.
  • PGE2 treatment led to a rapid, transient increase in intracellular cAMP levels.
  • Macrophage phagocytosis of Ig-opsonized erythrocytes remained unaffected, indicating specificity.
  • cAMP elevation induced changes in macrophage morphology, suggesting altered adhesive properties.

Conclusions:

  • Activation of cAMP signaling pathways by inflammatory mediators like PGs regulates macrophage phagocytosis of apoptotic cells.
  • This regulation plays a role in limiting tissue injury during inflammation.
  • Modulation of cAMP levels presents a potential therapeutic strategy for controlling inflammation resolution.

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