Pruzanski W, Saito S, Stylianos S, Jacobs H
Department of Medicine, Wellesley Hospital, University of Toronto, Ontario, Canada.
Inflammation. 1989 Apr;13(2):201-9. doi: 10.1007/BF00924790.
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.
单克隆IgM冷凝聚素(CA)能结合并在补体存在的情况下,对多种哺乳动物细胞具有细胞毒性。迄今为止,这些自身抗体对吞噬细胞功能能力的影响尚未得到研究。在此我们报告,含有单克隆IgM抗-I和抗-i CA的血清在37℃和24℃时能显著降低人外周血多形核细胞(PMN)的黏附性、吞噬作用、吞噬指数和细胞内杀菌活性。抗-i CA比抗-I更具活性。不具有CA活性的单克隆IgM血清可减少摄入细菌的总数,但对吞噬功能无其他影响。用抗-i和抗-I CA检测脐带、母体和成人PMN时,抑制程度没有差异。经色谱纯化的α-I和α-i CA在低至1mg/ml的浓度下就能显著抑制吞噬作用。外周血单核细胞的吞噬活性在18℃时受到CA的抑制,但在24℃或37℃时不受抑制。经色谱纯的IgM CA经胃蛋白酶消化或还原及烷基化后,其抑制活性完全丧失。因此,在生理温度下,单克隆IgM冷凝聚素会损害人吞噬细胞的各种吞噬功能。这可能会增加合成此类自身抗体患者的感染易感性。