MOUSE CRRY P65 IS A REGULATOR OF THE ALTERNATIVE PATHWAY OF COMPLEMENT ACTIVATION/

Like man, mouse has evolved a unique set of regulatory proteins which provide protection from complement-mediated damage to self membranes. The recently described mouse protein Crry/p65 has been shown to inhibi t classical complement pathway C3 deposition on cell membranes in whic h it is expressed. In two distinct experimental systems, we now furthe r delineate the regulatory activity of Crry/p65 and demonstrate its in hibitory effect on alternative complement pathway C3 activation. First , significant inhibition of mouse alternative pathway C3 deposition wa s demonstrated on neuraminidase-treated human K562 cells expressing re combinant Crry/p65. Second, using a baculovirus technique, recombinant Crry/p65 was synthesized as a soluble molecule and then purified. Thi s molecule was found to inhibit mouse C3 deposition on the surface of zymosan, a potent alternative complement pathway activator. These stud ies, combined with our earlier findings, demonstrate that Crry/p65 can regulate both the classical and alternative complement pathways. Crry /p65 must, therefore, exert its effects prior to, or at the level of, the C3 convertases, in a fashion similar to that of human membrane cof actor protein and/or decay-accelerating factor. These studies provide further proof of the hypothesis that Crry/p65 is an evolutionarily uni que, complement regulatory protein which has developed in mouse.