Activation of the alternative pathway of complement by human peripheral nerve myelin
Koski, C.L.; Vanguri, P.; Shin, M.L.
Journal of Immunology 134(3): 1810-1814
1985
ISSN/ISBN: 0022-1767 PMID: 2578522 Document Number: 246753
Destruction of peripheral nerve myelin (PNM) occurs as a consequence of a variety of pathologic conditions affecting the peripheral nervous system. In certain primary demyelinating neuropathies, several lines of evidence implicate complement in the pathogenesis of demyelination. Human PNM consumes complement in vitro in the absence of specific antibody or C1 activation. Activation of complement by PNM via the alternative pathway was shown by cleavage of C3 in normal human serum (NHS) and of B in C2-deficient serum (C2D-HS). Increasing consumption of hemolytic activity of C3 in Mg-EGTA[ethylene-bis-(oxyethylene-natrilo)tetraacetic acid]-treated NHS was also noted with increasing amounts of PNM. Pronase treatment of PNM abolished C3 consumption, suggesting that a protein component exposed on the surface of myelin participated in the alternative pathway activation. When PO, the major amphiphilic glycoprotein of PNM, was incorporated into artificial lipid bilayers, the PO-liposomes consumed C3 activity in NHS containing Mg-EGTA. Pronase treatment of PO-liposomes abolished C3 consumption to the level of control liposomes, indicating that PO was responsible for at least part of the activation seen with peripheral myelin.