A monoclonal antibody to sialophorin (CD43) induces homotypic adhesion and activation of human monocytes.
Treatment of human monocytes for 24-48 h with the anti-CD43 mAb L10 caused five- to sevenfold stimulation of hydrogen peroxide-producing capacity, an established characteristic of activated monocytes. Peroxide-producing capacity induced by L10 antibody (1.6 +/- 0.3 nmol H2O2/micrograms DNA/h) was comparable with that induced by IFN-gamma (1.3 +/- 0.4 nmol H2O2/micrograms DNA/h), but appeared more rapidly (maximal at 24 h) than in the IFN-gamma-treated monocytes (maximal at 48 h). Treatment of monocytes with L10 mAb also caused dramatic increase in aggregation (homotypic adhesion). Induction of monocyte aggregation by L10 mAb required incubation for 1-8 h in the presence of Mg2+ and was abrogated by TA-1, an anti-LFA-1-alpha mAb. Thus, L10-induced monocyte activation proceeds via a Mg2+-requiring aggregation stage involving LFA-1. Whereas the extent of monocyte aggregation induced by L10 mAb and by IFN-gamma were comparable, the L10-induced aggregation occurred more rapidly (maximal at 8 h) than the IFN-gamma-induced aggregation (maximal at 24 h). The more rapid appearance of aggregation and increased hydrogen peroxide capacity in L10-treated monocytes suggests that the L10-induced activation pathway is independent of IFN-gamma-and IFN-gamma-R dependent events. These findings suggest that the surface molecule CD43 is the receptor of an independent activation pathway that leads in lymphocytes to proliferation and in monocytes to activation.
Nong
Y H
YH
Department of Rheumatology and Immunology, Brigham and Women's Hospital, Boston, Massachusetts.
Remold-O'Donnell
E
E
LeBien
T W
TW
Remold
H G
HG
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D007700:Kinetics; D051917:Leukosialin; D008274:Magnesium / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D012795:Sialoglycoproteins
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D000943:Antigens, Differentiation; D051917:Leukosialin; C465014:SPN protein, human; D012795:Sialoglycoproteins; D006861:Hydrogen Peroxide; D008274:Magnesium; D002118:Calcium