Hydrolysis of myelin basic protein in human myelin by terminal complement complexes.
The participation of terminal complement complexes (TCC) in demyelination has been shown in rodent cerebellar cultures. Since TCC modulates activities of various membrane-associated enzymes and increases the level of cellular Ca2+ we investigated whether TCC could activate Ca2+-dependent neutral proteases in myelin that would lead to hydrolysis of myelin basic protein (BP). Addition of antibody and C7-deficient serum plus C7 to sealed myelin vesicles of two to six bilayers caused significant BP hydrolysis compared to the hydrolysis caused by antibody and C7-deficient serum. Significant hydrolysis occurred at the stage of C5b6,7 assembly, which increased in magnitude at the C5b6-8 stage. C5b6-9 formation did not enhance the effect of C5b6-8. BP hydrolysis by C5b6,7 did not require Ca2+ whereas the effect of C5b6-8/C5b6-9 was, in part, Ca2+-dependent. We postulated that TCC formation in myelin membranes causes activation of myelin-associated neutral proteases with subsequent hydrolysis of BP as a consequence of complement peptide insertion and channel formation. Such processes may alter the structure of myelin and augment the action of other inflammatory cells and their products in demyelinating diseases that could ultimately lead to the loss of myelin.
D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism*; D006461:Hemolysis; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D013116:Spinal Cord / Q000378:metabolism; D014357:Trypsin
D015938:Complement Membrane Attack Complex; D004676:Myelin Basic Protein; D003165:Complement System Proteins; D014357:Trypsin