Activation of monocytes via their Fc alpha R increases procoagulant activity.
There is increasing evidence in experimental models of glomerulonephritis, including IgA nephropathy, that macrophages accumulate within the affected kidneys. Increased procoagulant activity (PCA) consequent on the influx of these cells has been associated with the progression of kidney disease. We have studied the effect of activation of the monocyte Fc alpha receptor (Fc alpha R) on PCA. Immune complexes of immunoglobulin A (IgA) isotype formed in situ or the addition of aggregated IgA resulted in a dose-dependent increase of monocyte PCA. Maximal effect was achieved after 6 hours of incubation. PCA induced by Fc alpha R was consistent but was less than that observed after addition of endotoxin to monocyte monolayers or after activation via the Fc gamma R or mannose receptor. Specificity of the interaction of the ligands with Fc alpha R was shown; galactose inhibited effects mediated via the Fc alpha R but not via the Fc gamma R. Corticosteroids inhibited Fc alpha R monocyte-induced PCA. These results are likely to be relevant in the immunopathogenesis of IgA-mediated disease, particularly IgA nephropathy.
Keidan
I
I
Samuel Jared Kushnick Pediatric Immunology Laboratory, Israel.
Laufer
J
J
Shor
R
R
Farzam
N
N
Gitel
S
S
Passwell
J H
JH
D000936:Antigen-Antibody Complex / Q000502:physiology; D015703:Antigens, CD; D001779:Blood Coagulation Factors / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003907:Dexamethasone / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D011961:Receptors, Fc / Q000502:physiology*
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D001779:Blood Coagulation Factors; D003432:Cross-Linking Reagents; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; C045071:leukocyte procoagulant activity; D003907:Dexamethasone; D005690:Galactose