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The role of complement receptor type 1 (CR1, CD35) in determining the cellular distribution of opsonized immune complexes between whole blood cells: kinetic analysis of the buffering capacity of erythrocytes
Author(s) -
NIELSEN C. H.,
MATTHIESEN S. H.,
LYNG I.,
LESLIE R. G. Q.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00138.x
Subject(s) - opsonin , incubation , complement receptor , receptor , immune system , biology , immune complex , microbiology and biotechnology , complement system , antibody opsonization , immunology , antibody , biochemistry
Erythrocytes (E) express complement receptor, type 1 (CR1, CD35), by which they bind opsonized immune complexes (IC) in competition with leucocytes expressing higher numbers of CR1 as well as other complement‐ and Fc‐receptors. This may prevent inappropriate activation of phagocytic cells. We examined the distribution on whole blood cells of preformed tetanus toxoid (TT)/human anti‐TT IC, opsonized in situ in 80% autologous serum. Binding to E occurred rapidly and reflected the kinetics of C3‐fragment incorporation into the IC. Among eight donors, expressing 180–361 CR1 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 min. 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 polymorphonuclear leucocytes (PMN) by 61±26% after 30 seconds of incubation and 47±14% after 5 min. During the subsequent 10 min, this buffering capacity of E was essentially abolished. E restricted the initial IC‐binding to B cells by 73±19%, but from 3 min of incubation the presence 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‐uptake by B cells as well as PMN and monocytes, since CR1‐blockade inhibited the initial IC‐uptake by these populations in a preparation of isolated leucocytes suspended in serum by ≥84% after 30 seconds of incubation. We conclude, that E exert a substantial buffering effect on the IC‐deposition on PMN, monocytes and B cells, while CR1 is the dominant receptor in the uptake by these cells. However, this effect is short‐lived and less than expected from the proportion of IC bound to E. Moreover, E are efficient processors of IC‐attached 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 may play a role in preventing phagocyte activation via CR3.