A phagocytic challenge with IgG-coated erythrocytes depresses macrophage respiratory burst and phagocytic function by different mechanisms.
A phagocytic challenge with IgG-coated erythrocytes (EIgG) previously has been shown to cause impaired macrophage respiratory burst capacity and FcgammaR-mediated phagocytic function. Because both the respiratory burst and FcgammaR-mediated phagocytosis are dependent on the release of arachidonate (AA), we evaluated the effects of impaired AA release on the depression of macrophage function caused by a phagocytic challenge. Challenge with EIgG caused a depression of A23187-stimulated AA release that was associated with impaired phorbol myristate acetate (PMA)-stimulated H2O2 production and FcgammaR-mediated phagocytic function. In contrast, challenge with IgG-coated glass beads (BIgG) had no effect on either AA release or H2O2 production but did depress phagocytic function. Exogenous AA prevented the depression of H2O2 production but had no effect on phagocytic function. Phospholipase A2 (PLA2) activity was depressed under conditions where AA release was impaired. The depression of phagocytic function was correlated with a depression of both EIgG binding and FcgammaR expression. Thus, a phagocytic challenge with EIgG results in macrophage dysfunction by depressing PLA2 activity and depleting FcgammaR.
Raley
M J
MJ
Department of Basic and Pharmaceutical Sciences, Albany College of Pharmacy, New York, USA.
Lennartz
M R
MR
Loegering
D J
DJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley; D017452:Receptors, IgG / Q000378:metabolism; D016897:Respiratory Burst
D007074:Immunoglobulin G; D017452:Receptors, IgG; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054467:Phospholipases A2