Influence of monoclonal IgM cold agglutinins on adhesiveness, phagocytosis, and bactericidal activity on human granulocytes and monocytes.
Monoclonal IgM cold agglutinins (CA) bind and, in the presence of complement, are cytotoxic to various mammalian cells. The impact of these autoantibodies on functional capacity of phagocytes has not been studied until now. Herein we report that sera with monoclonal IgM anti-I and anti-i CA significantly reduce adhesiveness, phagocytosis, phagocytic index, and intracellular bactericidal activity of human peripheral blood polymorphonuclear cells (PMNs) at 37 degrees C and 24 degrees C. Anti-i CA were more active than anti-I. Sera with monoclonal IgMs without CA activity reduced the total number of ingested bacteria but otherwise had no effect on phagocytic functions. There was no difference in the degree of inhibition when anti-i and anti-I CA were tested against cord, maternal, and adult PMNs. Chromatographically purified a-I and a-i CA inhibited markedly phagocytosis in concentrations as low as 1 mg/ml. Phagocytic activity of peripheral blood monocytes was inhibited by CA at 18 degrees C but not at 24 degrees C or 37 degrees C. Pepsin digestion or reduction and alkylation of chromatographically pure IgM CA abolished completely their inhibitory activity. Thus, in physiological temperatures, monoclonal IgM cold agglutinins impair various phagocytic functions of human phagocytes. It may add to the susceptibility to infections in patients in which such autoantibodies are synthesized.
Department of Medicine, Wellesley Hospital, University of Toronto, Ontario, Canada.
W
W
Pruzanski
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S
Saito
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S
Stylianos
H
H
Jacobs
D000373:Agglutinins / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001770:Blood Bactericidal Activity; D002448:Cell Adhesion; D002478:Cells, Cultured; D003080:Cold Temperature; D003450:Cryoglobulins; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis
D000373:Agglutinins; D000911:Antibodies, Monoclonal; D003450:Cryoglobulins; D007075:Immunoglobulin M; C029443:cold agglutinins