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001-es BibID:	BIBFORM038627
035-os BibID:	PMID:8933821
Első szerző:	Brahmi, Z.
Cím:	Synergistic inhibition of human cell-mediated cytotoxicity by complement component antisera indicates that target cell lysis may result from an enzymatic cascade involving granzymes and perforin / Brahmi Z., Csipo I., Bochan M. R., Su B., Montel A. H., Morse P. A.
Dátum:	1995
Megjegyzések:	A widely accepted theory of lymphocyte-mediated cytotoxicity (CMC) proposes that upon effector cell (EC) and target cell (TC) interaction, release of perforin, serine proteases and other lytic moieties contained within cytoplasmic granules results in TC lysis. Complement activation and the activation of the various enzymatic activities associated with cytotoxic granules have strikingly similar modes of action and both lead to pore formation in their respective targets. We report here that by using antisera to early and late complement components we were able to inhibit CTL, NK and ADCC cytotoxicity up to 100%, even though binding of EC to TC was unaffected. Furthermore, we showed that addition of C1q or C1s (two serine proteases) antisera to C9 antisera, at titers too low to inhibit separately, resulted in synergistic inhibition of CMC. Anti-C1s together with anti-C1q (or anti-C8 with anti-C9) did not result in synergy. This finding supports a cascade model of activation for lytic molecules released from EC. In addition, we demonstrated that anti-C1q and anti-C1s bind to proteins in the 30-kD region and anti-C9 binds to proteins in the 70-kD region, coinciding with published molecular weights of granzymes and perforin, respectively. Finally, lytic ability of purified granules was also inhibited by complement antisera, further suggesting that activation occurs outside of TC. Taken as a whole, these data indicate that TC lysis may be the result of a cascade of events involving granzymes and perforin, analogous to that seen with the complement system.
Tárgyszavak:	Orvostudományok Egészségtudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény 0 (Antibodies, Monoclonal) 0 (Complement Membrane Attack Complex) 0 (Membrane Glycoproteins) 0 (Pore Forming Cytotoxic Proteins) 0 (Serine Proteinase Inhibitors) 126465-35-8 (Perforin) 9007-36-7 (Complement System Proteins) EC 3.4.21.- (Serine Endopeptidases) Antibodies, Monoclonal/immunology/pharmacology Antibody-Dependent Cell Cytotoxicity/drug effects/immunology Binding, Competitive/immunology Burkitt Lymphoma Complement Membrane Attack Complex/immunology Complement System Proteins/immunology Cytotoxicity, Immunologic/drug effects Drug Synergism Enzyme Activation Humans Immunity, Cellular/drug effects Killer Cells, Natural/drug effects/immunology Leukemia, Erythroblastic, Acute Membrane Glycoproteins/analysis/antagonists & inhibitors Perforin Pore Forming Cytotoxic Proteins Serine Endopeptidases/analysis Serine Proteinase Inhibitors/immunology/pharmacology T-Lymphocytes, Cytotoxic/drug effects/immunology Tumor Cells, Cultured
Megjelenés:	Natural Immunity. - 14 : 5-6 (1995), p. 271-285. -
További szerzők:	Bochan, M. R. Su, B. Montel, A. H. Morse, P. A. Csípő István (1953-) (vegyész)
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