Peripheral nerve CR1 express in situ cofactor activity for degradation of C3b.

Adsorption of sheep erythrocytes (E) sensitized with IgM antibodies (A) and C3b (EAC3b) to C3b/C4b receptors (CR1) in cryostat sections of human myelinated nerves was studied using the closed chamber technique. The adsorption was stable for at least 3 h at 37 degrees C. In the presence of purified factor I, the indicator cells detached from the sections after 40 min at 37 degrees C. Factor H was not required. The release was not due to loss of CR1 activity in the sections. The detached indicator cells were negative in the immune adherence test and were agglutinated by antibody to C3d, but not by antibody to C3c. Western blot of the detached indicator cells revealed the presence of C3d and C3c was found in the chamber fluid. Accordingly, detachment of the indicator cells was due to degradation of C3b to C3d with the release of C3c into the chamber fluid. Protease inhibitors did not prevent the detachment of the indicator cells. EAC3b incubated with sections of myelinated nerves pre-incubated with anti-CR1 antibody or with sections of unmyelinated nerves which contain functionally inactive CR1 were not degraded. The results therefore indicate that CR1 in situ in myelinated nerves can provide the necessary cofactor activity for factor I-mediated degradation of C3b to C3d and C3c.