Modulation of the human monocyte binding site for monomeric immunoglobulin G by activated Hageman factor.
Macrophage Fc gamma receptors play a significant role in inflammation and host defense. One monocyte/macrophage Fc gamma receptor, Fc gamma RI, the binding site for monomeric IgG, appears to be especially responsive to modulatory signals by hormones and mediators. Since Factor XIIa is generated during inflammation, we studied the effect of XIIa on Fc gamma RI. Factor XIIa, in a concentration-dependent manner (0.01-0.19 microM), reduced the number of monocyte binding sites for monomeric IgG up to 80% without altering the affinity of binding. Its precursor, Factor XII, and the low molecular weight fragment of XIIa, lacking most of the heavy chain region, did not reduce the expression of Fc gamma RI. Neither corn trypsin inhibitor (36 microM) nor diisopropylfluorophosphate (3.6 mM) diminished the effect of Factor XIIa on Fc gamma RI, although each completely inhibited the coagulant and amidolytic activity contained on the light chain of Factor XIIa. Protein synthesis was not a requirement for this effect of Factor XIIa, nor was internalization of Fc gamma RI necessary. In contrast to similar concentrations of IgG, Factor XIIa failed to displace significantly monomeric IgG from the monocyte surface, suggesting that Factor XIIa does not directly compete for Fc gamma RI. The data suggest that the heavy chain of XIIa, which contains domains that may have cell hormone activity, also contains a domain that regulates Fc gamma RI on monocytes. In addition to other hormones and mediators, Factor XIIa may serve a regulatory function in modulating Fc gamma receptor expression during inflammation.
Chien
P
P
University of Pennsylvania School of Medicine and Cancer Center, Philadelphia 19104.
Pixley
R A
RA
Stumpo
L G
LG
Colman
R W
RW
Schreiber
A D
AD
D001665:Binding Sites; D005174:Factor XII / Q000494:pharmacology*; D015956:Factor XIIa; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007531:Isoflurophate / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D010940:Plant Proteins / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism; D012697:Serine Endopeptidases / Q000494:pharmacology*
D007074:Immunoglobulin G; D010940:Plant Proteins; D011961:Receptors, Fc; C052160:trypsin inhibitor, Zea mays; D007531:Isoflurophate; D005174:Factor XII; D012697:Serine Endopeptidases; D015956:Factor XIIa