Lysis of complement-sensitive Entamoeba histolytica by activated terminal complement components. Initiation of complement activation by an extracellular neutral cysteine proteinase.
Activation of complement by Entamoeba histolytica may be initiated by the extracellular 56-kD neutral cysteine proteinase which cleaves the alpha chain of C3. To determine the relationship between the fluid-phase activation of complement and our observation that only strains isolated from patients with invasive disease are resistant to complement-mediated lysis, we investigated the fate of C3 with recent amebic isolates. When 125I-C3 was incubated with trophozoites in serum, C3 in the fluid phase was cleaved to C3b or C3bi, but the alpha chain of the C3 molecules on the cell surface appeared intact. Since the lysis of nonpathogenic strains takes place in the absence of bound C3b, we demonstrated that this reaction occurs by reactive lysis initiated in the fluid phase: (a) the killing of nonpathogenic strains was enhanced when alternative pathway activation was accelerated by the addition of cobra venom factor; (b) non-pathogenic strains were lysed by purified terminal components; and (c) sera incubated with pathogenic E. histolytica produced passive lysis of chicken erythrocytes. These results demonstrate for the first time that complement-sensitive E. histolytica are lysed by activation of the terminal complement components in the fluid phase where the 56-kD neutral cysteine proteinase cleaves C3, and not by the surface deposition of activated C3.
Reed
S L
SL
Department of Medicine, UCSD Medical Center 92103.
Gigli
I
I
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D003167:Complement Activation; D003176:Complement C3 / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004748:Entamoeba histolytica / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D066298:In Vitro Techniques
D000953:Antigens, Protozoan; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D015853:Cysteine Proteinase Inhibitors; D003546:Cysteine Endopeptidases