Induction of IL-1 release through stimulation of the C3b/C4b complement receptor type one (CR1, CD35) on human monocytes.
Soluble polymerized human C3b and C3b bound to Sepharose induced the production of cell-associated IL-1 and the extracellular release of IL-1 activity from cultured human adherent monocytes. Cultures were performed in serum-free conditions in the presence of polymyxin B and of the PG synthesis inhibitor indomethacin. Induction of intracellular IL-1 activity was associated with that of IL-1 alpha and IL-1 beta Ag. Biologically active released IL-1 was IL-1 beta. Monomeric C3b induced cell-associated IL-1 but not the release of IL-1 from monocytes. IL-1 production was also induced by stimulation of CR1 on adherent monocytes with anti-C3b receptor (CR1) antibody. The ability of multivalent C3b to induce IL-1 production could be dissociated from that of possibly contaminating LPS by several criteria including: the lack of detectable LPS in purified C3b; functional inhibition of LPS in cultures with polymyxin B; the lack of induction of extracellular IL-1 by C3b monomer; a correlation between the expression of CR1 on monocytes and the monocytic response to C3b; a dissociation between the expression of CR1, and the expression of LPS binding sites and the IL-1 response of monocytes to endotoxin. Induction of IL-1 represents a novel pathway by which C3b-CR1 interactions may modulate the immune response.
Bacle
F
F
INSERM U28, Hôpital Broussais, Paris, France.
Haeffner-Cavaillon
N
N
Laude
M
M
Couturier
C
C
Kazatchkine
M D
MD
D002478:Cells, Cultured; D003179:Complement C3b / Q000502:physiology; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b
D007375:Interleukin-1; D008024:Ligands; D008070:Lipopolysaccharides; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003179:Complement C3b