THE ROLE OF COMPLEMENT RECEPTOR-TYPE-1 (CR-1, CD35) IN DETERMINING THE CELLULAR-DISTRIBUTION OF OPSONIZED IMMUNE-COMPLEXES BETWEEN WHOLE-BLOOD CELLS - KINETIC-ANALYSIS OF THE BUFFERING CAPACITY OF ERYTHROCYTES
Ch. Nielsen et al., THE ROLE OF COMPLEMENT RECEPTOR-TYPE-1 (CR-1, CD35) IN DETERMINING THE CELLULAR-DISTRIBUTION OF OPSONIZED IMMUNE-COMPLEXES BETWEEN WHOLE-BLOOD CELLS - KINETIC-ANALYSIS OF THE BUFFERING CAPACITY OF ERYTHROCYTES, Immunology, 90(1), 1997, pp. 129-137
Erythrocytes (E) express complement receptor, type 1 (CR1, CD35), by w
hich they bind opsonized immune complexes (IC) in competition with leu
cocytes expressing higher numbers of CR1 as well as other complement-
and Fc-receptors. This may prevent inappropriate activation of phagocy
tic cells. We examined the distribution on whole blood cells of prefor
med tetanus toroid (TT)/human anti-TT IC, opsonized in situ in 80% aut
ologous serum. Binding to E occurred rapidly and reflected the kinetic
s of C3-fragment incorporation into the IC. Among eight donors, expres
sing 180-361 CRI per E, >90% of the cell-bound IC were associated with
E from 1 to 5 min of incubation, decreasing to 12 +/- 13% after 40 mi
n. Upon comparison of the IC-binding to leucocytes in whole blood with
that of isolated leucocytes we found that E, despite their extensive
early complex uptake, only reduced the IC-deposition on polymorphonucl
ear leucocytes (PMN) by 61 +/- 26% after 30 seconds of incubation and
47 +/- 14% after 5 min,During the subsequent 10 min, this buffering ca
pacity of E was essentially abolished. E restricted the initial IC-bin
ding to B cells by 73 +/- 19%, but from 3 min of incubation the presen
ce of E promoted, in a CR1-dependent manner, a progressive uptake via
CR2 by the B cells. CR1 was the dominant receptor in the early IC-upta
ke by B cells as well as PMN and monocytes, since CR1-blockade inhibit
ed the initial IC-uptake by these populations in a preparation of isol
ated leucocytes suspended in serum by greater than or equal to 84% aft
er 30 seconds of incubation. We conclude, that E exert a substantial b
uffering effect on the IC-deposition on PMN, monocytes and B cells, wh
ile CR1 is the dominant receptor in the uptake by these cells. However
, this effect is short-lived and less than expected from the proportio
n of IC bound to E. Moreover, E are efficient processors of IC-attache
d C3b/iC3b fragments to C3dg as indicated by a pronounced enhancement
by E of IC-uptake via CR2 on B cells. We propose that this mechanism m
ay play a role in preventing phagocyte activation via CR3.