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Surface contact modulation of inflammatory macrophage antibody dependent cytotoxicity and prostanoid release
Author(s) -
Gudewicz Paul W.,
Frewin Mary Beth
Publication year - 1991
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041490204
Subject(s) - fibronectin , extracellular matrix , extracellular , chemistry , macrophage , microbiology and biotechnology , biochemistry , biology , in vitro
Adherence to extracellular matrix proteins modulates the functional and secretory activities of mononuclear phagocytes, although the mechanisms regulating these adherence‐dependent changes are poorly understood. In this study, the ability of rat inflammatory peritoneal macrophages (PM) to adhere to an endothelial cell‐derived extracellular matrix or a denatured collagen/fibronectin‐coated surface and perform antibody dependent cell cytotoxicity (ADCC) and secrete reactive oxygen intermediates was compared with PM adherent to tissue culture plastic. Prostaglandin E 2 (PGE 2 ) and thromboxane B 2 (TxB 2 ), two major cyclooxygenase products released by inflammatory macrophages, were also measured by PM adherent to the protein coated surfaces. Rat exudate PM were equally adherent to tissue culture plastic or wells coated with either endothelial cell derived matrix or denatured collagen (gelatin)/fibronectin. PM adherent to a denatured collagen/fibronectin‐coated wells demonstrated significantly less cytolytic activity (15 ± 2% lysis) when compared with either tissue culture plastic adherent PM (43 ± 7% lvsis) or PM adherent to extracellular matrix (59 ± 11% lysis). PM adherent to extracellular matrix released twofold more TxB 2 than plastic adherent PM, while PM adherent to denatured collagen/fibronectin released 40% more PGE 2 than cells adherent to tissue culture plastic or 80% more PGE 2 than PM adherent to the extracellular matrix. PM adherent to denatured collagen/fibronectin release less superoxide anion (27 ± .9 nmoles/10 6 PM) than PM adherent to either tissue culture plastic (43 ± 1 nmoles/10 6 PM) or the extracellular matrix (60 ± 0.5 nmoles/10 6 PM). Furthermore, incubation of plastic adherent PM with exogenous PGE 2 reduced superoxide production in a dosedependent manner. These results demonstrate that the inhibition of ADCC and secretion of reactive oxygen intermediates by PM adherent to a denatured collagen/fibronectin surface correlated with an increased release of the immunosuppressive prostanoid PGE 2 . Furthermore, the addition of exogenous PGE 2 to plastic adherent PM reproduced the depression in ADCC and superoxide anion production observed by PM adherent to a denatured collagen/fibronectin surface. These studies suggest that the increased production and release of PGE 2 by inflammatory macrophages adherent to a denatured collagen surface may act to suppress cytotoxic mechanisms and thereby constitutes part of an autocrine feedback mechanism regulating macrophage function during wound injury.