Lysosomal Enzyme Release from Human Leukocytes: Mediation by the Alternate Pathway of Complement Activation

Abstract The alternate pathway of complement activation has recently assumed an important role in the mediation of inflammation and tissue injury. We have found that complement activated via this pathway interacts with human polymorphonuclear leukocytes (PMN) in the absence of particulates and stimulates the selective release of lysosomal enzymes. Fresh human serum, after treatment with zymosan or cobra venom factor, yields a fluid phase component which induces cytochalasin B-treated PMN to release β-glucuronidase without leakage of cytoplasmic lactate dehydrogenase. Involvement of the alternate pathway of complement activation is evidenced by failure of serum to yield enzyme-releasing activity after pretreatment with rabbit antihuman C3 proactivator, 0.01 M EDTA but not 0.01 M EDTA, 0.02 M salicylaldoxime, 0.02 M hydrazine or by heating to 56°C for 30 min. Levels of C3 proactivator in treated sera correlated inversely with and perturbs the PMN plasma membrane sufficiently to cause lysosomal membrane perturbation, fusion, and ultimately lysosomal enzyme extrusion by a process of “reverse endocytosis.”