title: Activation of the alternative pathway of complement by human peripheral nerve myelin.
abstract: 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. In this study we demonstrate that human PNM consumes complement in vitro in the absence of specific antibody or C1 activation. Furthermore, 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-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 P0, 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 P0 was responsible for at least part of the activation seen with peripheral myelin.
authors.forename: C L
authors.initials: CL
authors.lastname: Koski
authors.forename: P
authors.initials: P
authors.lastname: Vanguri
authors.forename: M L
authors.initials: ML
authors.lastname: Shin
mesh_terms: D000818:Animals; D002420:Cauda Equina; D003167:Complement Activation; D003172:Complement C1 / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D003168:Complement Fixation Tests; D003170:Complement Pathway, Alternative; D006461:Hemolysis; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D008081:Liposomes / Q000378:metabolism; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D003172:Complement C1; D003176:Complement C3; D008081:Liposomes; D018993:Myelin P0 Protein; D009185:Myelin Proteins; D011415:Complement Factor B