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Inhibition of immune complex-mediated activation of complement

Effects of agents modulating activation of, and the activated Cl complex

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Abstract

Several known chemical compounds were shown to selectively inhibit the interaction between immune aggregates and Clq, the activation of Clr-Cls complex by immune aggregate-bound C1q, and the esterolytic activity of the activated Cls,\(\overline {\operatorname{CLs} } \). These reactions are relevant to the functions of the first complement component, Cl, and its activation induced by immune complexes. The effects of these inhibitors on tissue injury mediated by immune complex-induced complement activation, such as immune hemolysis, passive cutaneous anaphylaxis, and experimental glomerulonephritis were examined. The results suggest an approximate correlation between the activity shown on the molecular level and that obtained in vivo. One such compound, suramin, was shown to be an effective inhibitor of PCA and the proteinuria manifestation of EGN while not affecting antibody fixation to tissue or histamine-mediated skin reaction. These results suggest that effective suppression of the initial steps of complement activation may be of value in controlling immune complex-mediated tissue injuries in disease.

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Abbreviations

PCA:

passiave cutaneous anaphylaxis in guinea pigs

BSA:

bovine serum albumin

PBS:

0.15 M NaCl containing 10 mM sodium phosphate buffer or 10 mM Tris-HCl buffer, pH 7.40

SDS:

sodium dodecyl sulfate

PAGE:

polyacrylamide gel electro Phoresis

EACA:

epsilon-aminocaproic acid

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  1. Department of Immunology, Merck Sharp & Dohme Research Laboratories, 07065, Rahway, New Jersey

    Daniel S. Fletcher & Tsau -yen Lin

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  1. Daniel S. Fletcher
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Fletcher, D.S., Lin, T.y. Inhibition of immune complex-mediated activation of complement. Inflammation 4, 113–123 (1980). https://doi.org/10.1007/BF00914108

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