Alpha 2 macroglobulin-proteinase complexes stimulate prostaglandin E2 synthesis by peritoneal macrophages.
alpha 2-Macroglobulin is a proteinase inhibitor which is converted from its native form into an electrophoretically "fast" form by reaction with a proteinase or methylamine. All alpha 2M "fast" forms bind to a specific high-affinity receptor on macrophages. alpha 2M "fast" forms inhibit the interferon-gamma (IFN)-induced increase in macrophage Ia expression. This study examined whether alpha 2M-proteinase complexes alter prostaglandin (PG) E2 synthesis, and whether PGE2 mediates alpha 2M "fast" forms effects on macrophage Ia expression. Culture with alpha 2M "fast" forms increased PGE2 accumulation in the medium over control values in a dose-dependent manner. Culture with IFN alone did not increase PGE2 levels, but potentiated the effect of alpha 2M-proteinase complexes on PGE2 levels. Inhibition of PGE2 synthesis did not alter the inhibitory effect of alpha 2M-proteinase complexes on IFN-induced Ia expression. However, exogenous PGE2 did suppress IFN-induced Ia expression. Thus, alpha 2M-proteinase complexes increase macrophage PGE2 synthesis, but increased synthesis of PGE2 or other cyclooxygenase products is not the mediator of antagonism of IFN-induced Ia expression by alpha 2M-proteinase complexes.
Hoffman
M
M
Department of Laboratory Medicine, Durham Veterans Administration Medical Center, NC.
Pizzo
S V
SV
Weinberg
J B
JB
D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010537:Peritoneum; D014357:Trypsin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D000511:alpha-Macroglobulins; D014357:Trypsin; D015232:Dinoprostone; D007052:Ibuprofen