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Sublytic complement attack protects tumor cells from lytic doses of antibody and complement
Y Reiter1, A Ciobotariu, Z Fishelson
1Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
European Journal of Immunology
|May 1, 1992
Summary
Sublytic doses of the membrane attack complex (MAC) protect human leukemic cells from complement-mediated lysis. This "complement-induced protection" requires RNA and protein synthesis, and extracellular calcium ions.
Area of Science:
- Immunology
- Cell Biology
Background:
- Sublytic doses of the membrane attack complex (MAC) stimulate metabolically active cells.
- Complement activation plays a crucial role in cellular defense mechanisms.
Purpose of the Study:
- To investigate the phenomenon of "complement-induced protection" in human leukemic cells.
- To elucidate the molecular mechanisms underlying complement-induced resistance.
Main Methods:
- Pretreatment of K562 and HL-60 cells with sublytic doses of antibody and human serum.
- Assessment of cell resistance to lytic complement concentrations.
- Inhibition studies using actinomycin D and cycloheximide.
- Analysis of bound complement components (C3, C9).
- Investigation of the role of extracellular calcium (Ca2+).
Main Results:
- Sublytic MAC doses induce resistance to lytic complement concentrations in K562 and HL-60 cells.
- This protection is dependent on RNA and protein synthesis, as well as extracellular Ca2+.
- C7- and C8-deficient sera were ineffective unless reconstituted.
- Similar amounts of C3 and C9 were deposited on protected and control cells.
- Protected cells regained sensitivity after 3-8 hours of culture.
- Protection was observed across different species.
Conclusions:
- Sublytic complement activation triggers a protective cellular response.
- Complement-induced protection involves de novo RNA and protein synthesis and calcium signaling.
- This phenomenon offers a novel perspective on complement-mediated cellular interactions.