Killing of human melanoma cells by the membrane attack complex (MAC) as a function of its molecular composition
The efficiency of the MAC in causing membrane damage and lysis of M21 cells was determined varying the C9:C8 molar ratio. C8,C9-depleted serum was reconstituted with radio-labeled C8 and C9 in kinetic and dose-response analyses. C5b-8 was sufficient to cause membrane leakiness, determined by /sup 86/Rb release and propidium iodide (PI) uptake, and this membrane damage was largely reversible. Cell killing was effected at high C5b-8 density as evidenced by /sup 51/Cr release and PI uptake with enhancement by C9. C5b-8 dependent cytolysis showed a lag between C8 binding and functional channel formation and increased with C8 uptake, suggesting cooperativity of C5b-8 in channel formation. With limiting numbers of bound C8 molecules, C9 binding and channel formation proceeded without lag. Saturation of C9 binding sites was observed at an average C9:C8 ratio of 6:1. By electron microscopy (EM), circular membrane lesions were visualized at a C9:C8 ratio of 3:1 or higher. Maximal cytolytic efficiency of MAC was observed at lower ratios at which ultrastructural lesions could not be detected. These results suggest that M21 cells can be killed by C5b-8 and that killing is maximized by amounts of C9 insufficient for poly C9 formation as detected by EM.
- Research Organization:
- Research Institute of Scripps Clinic and UCSD Medical Center, La Jolla, CA
- OSTI ID:
- 5495592
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL ISOTOPES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CELL CONSTITUENTS
CELL KILLING
CELL MEMBRANES
CHROMIUM 51
CHROMIUM ISOTOPES
COMPLEMENT
DAYS LIVING RADIOISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
ELECTRON MICROSCOPY
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LYSIS
MELANOMAS
MEMBRANE PROTEINS
MEMBRANES
MICROSCOPY
MINUTES LIVING RADIOISOTOPES
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RUBIDIUM 86
RUBIDIUM ISOTOPES