Immunology 2002 Jul;106(3):381-8 Related Articles, Books, LinkOut


Effects of C-reactive protein and pentosan polysulphate on human complement
activation.

Klegeris A, Singh EA, MCGeer PL.

Kinsmen Laboratory of Neurological Research, University of British Columbia,
Vancouver, BC, Canada.

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 microg/ml as
heparin, dextran sulphate, compstatin and fucoidan. PPS may have practical
application as a C inhibitor.

PMID: 12100726 [PubMed - in process]