CD59 HOMOLOG REGULATES COMPLEMENT-DEPENDENT CYTOLYSIS OF RAT SCHWANN-CELLS

Antibody (Ab) sensitized sciatic nerve Schwann cells (SchC) of 2-day-o ld rats (SchC/2d) were significantly more susceptible to cytolysis by both heterologous, guinea pig (GP), and homologous rat serum complemen t (40 +/- 3.8% and 21.2 +/- 3.1%, respectively) than SchC of 6-day-old rats (SchC/6d) (7.9 +/- 5.9% and 2.6 +/- 3.1%, respectively). To dete rmine if resistance to complement (C)-mediated cytolysis correlated wi th expression of membrane proteins which regulate C activation, we use d Western blot and FAGS analysis. Binding of specific polyclonal Ab de monstrated similar concentrations of Crry, a regulator of C3 convertas e formation, on plasma membranes of SchC 2d and 6d. During C activatio n, both C3b deposition and iC3b formation were greater on SchC/6d than on SchC/2d and the C3b deposition did not correlate with enhanced cyt olysis. In contrast, 2.1-fold more rat CD59, a regulator of C8 and C9 incorporation into C5b-9, detected with Western blot on SchC/6d compar ed with SchC/2d was confirmed by FAGS. Further, both rat and GP C8/C9 lysed SchC/2d expressing human C5b-7 (20.1 +/- 3.7 and 21.6 +/- 4.7%, respectively), while only GP C8/C9 caused cytolysis of 10.7 +/- 4.3% S chC/6d expressing hu C5b-7 and rat C8/C9 did not (0.5 +/- 0.5%). Prein cubation of SchC/d with an F(ab)(2) fragment of an mAb to rCD59 with b locking capacity, increased cytolysis mediated by rat serum C more tha n 6-fold to 16.7 +/- 3.0% but only 1.7-fold (maximum cytolysis 37.4 +/ - 11.2%) in SchC/2d. Our, data suggest that expression of rat CD59 on SchC increased almost two-fold between postnatal days 2 and 6, and thi s increased expression on more terminally differentiated SchC is a sig nificant factor in regulating terminal complement complex formation an d limiting cytolysis of rat SchC by homologous serum complement.