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Effects of C‐reactive protein and pentosan polysulphate on human complement activation
Author(s) -
Klegeris AndIs,
Singh Edith A.,
MCGeer Patrick L.
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01425.x
Subject(s) - complement system , chemistry , fucoidan , antibody , xanthine oxidase , reactive oxygen species , in vitro , biochemistry , pharmacology , microbiology and biotechnology , immunology , enzyme , medicine , biology , polysaccharide
Summary Complement (C) activation is believed to play an adverse role in several chronic degenerative disease processes, including atherosclerosis, myocardial infarction and Alzheimer's disease. We developed several in vitro quantitative assays to evaluate processes which activate C in human serum, and to assess candidates which might block that activation. Binding of C‐reactive protein (CRP) to immobilized cell surfaces was used as a tissue‐based method of activation, while immunoglobulin G in solution was used as a surrogate antibody method. Activation was assessed by deposition of C fragments on fixed cell surfaces, or by capture of C5b‐9 from solution. We observed that several cell lines, including SH‐SY5Y, U‐937, THP‐1 and ECV304, bound CRP and activated C following attachment of cells to a plastic surface by means of air drying. Treatment of human neuroblastoma SH‐SY5Y cells with the reactive oxygen intermediates generated by xanthine (Xa) – xanthine oxidase (XaOx) prior to air drying or by hydrogen peroxide solutions after air drying, enhanced C activation, possibly through oxidation of the cell lipid membrane. Several C inhibitors were tested for their effectiveness in blocking these systems. Pentosan polysulphate (PPS), an orally active agent, blocked C activation in the same concentration range of 1–1000 µg/ml as heparin, dextran sulphate, compstatin and fucoidan. PPS may have practical application as a C inhibitor.