The Journal of Immunology · 1973 · 187 citations · 0 references
Veterinary MedicineImmunologyPathologyImmunopathologyInflammationInnate ImmunityComplement SystemComplement-mediated InjuryImmune PhysiologyImmune-mediated InjuryInflammatory MediatorsLeukocyte RecruitmentComplement Activation PathwaysComplement In ImmunityComplement-mediated InflammationEnzyme ActivityEnzymesLysosomal Enzyme TraffickingLysosomal Membrane FusionTissue Injury Response
The alternate complement pathway plays a key role in mediating inflammation and tissue injury. Serum treated with zymosan or cobra venom factor generates a fluid‑phase component that, through the alternate complement pathway, triggers β‑glucuronidase release from cytochalasin B‑treated PMN without cytoplasmic leakage, as loss of activity after C3 proactivator or EDTA treatment demonstrates. Complement activation via the alternate pathway induces selective lysosomal enzyme release from PMN through reverse endocytosis, with higher C3 proactivator levels correlating with membrane perturbation and enzyme extrusion.
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.”