Zinc ions inhibit factor I-mediated release of CR1-bound immune complexes and degradation of cell-bound complement factors C3b and C4b.
ZnCl2 exerted a dose-dependent inhibition of citrate-phosphate-dextrose (CPD) plasma-induced release of 125I-labelled BSA-anti-BSA immune complexes (IC) bound to complement receptor type 1 (CR1, CD35) in human whole blood. Maximal inhibition was observed at 10 mM of ZnCl2. Furthermore, the release of IC bound to erythrocyte (E)-CR1 by purified factor I, factor I-deficient serum plus purified factor I, or normal human serum was reduced by approximately 90%, 64%, and 52%, respectively, in the presence of 10 mM ZnCl2. The effect of ZnCl2 on factor I-mediated degradation of cell-bound C3b/C4b was also investigated employing CPD blood or E from a factor I-deficient donor. These cells expressed covalently bound C3b and C4b as demonstrated by a simple agglutination technique. Upon incubation of CPD whole blood with purified factor I, or of E with purified factor I or normal CPD plasma, the C-fragments were cleaved and the cells were no longer agglutinated by antibodies to C3c and C4c. The presence of ZnCl2 prevented this factor I-mediated degradation of C3b and C4b, as evidenced by the unaffected agglutination of the cells by the antibodies. We conclude that ZnCl2 inhibited factor I activity since: (1) release of complement-preopsonized IC from E-CR1 by purified factor I was markedly inhibited (90%) in the presence of ZnCl2, (2) preincubation of the cells with ZnCl2 caused only a moderate inhibition (32-38%) of the IC release, and (3) degradation by purified factor I of covalently cell-bound C3b and C4b was abrogated in the presence of 10 mM ZnCl2.
Jepsen
H H
HH
Institute of Medical Microbiology, Odense University, Denmark.
Teisner
B
B
Svehag
S E
SE
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism*; D015935:Complement C4b / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000037:antagonists & inhibitors*; D006801:Humans; D011817:Rabbits; D011951:Receptors, Complement / Q000378:metabolism*; D017463:Receptors, Complement 3b; D015032:Zinc / Q000494:pharmacology*
D000936:Antigen-Antibody Complex; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003179:Complement C3b; D015935:Complement C4b; D005340:Fibrinogen; D015032:Zinc