CD23 regulates monocyte activation through a novel interaction with the adhesion molecules CD11b-CD18 and CD11c-CD18.
CD23 is expressed on a variety of haemopoietic cells and displays pleiotropic activities in vitro. We report that in addition to CD21 and IgE, CD23 interacts specifically with the CD11b and CD11c, the alpha chains of the beta 2 integrin adhesion molecule complexes CD11b-CD18 and CD11c-CD18, on monocytes. Full-length recombinant CD23 incorporated into fluorescent liposomes was shown to bind to COS cells transfected with cDNA encoding either CD11b-CD18 or CD11c-CD18 but not with CD11a-CD18. The interaction was specifically inhibited by anti-CD11b or anti-CD11c, respectively, and by anti-CD23 MAbs. The functional significance of this ligand pairing was demonstrated by triggering CD11b and CD11c on monocytes with either recombinant CD23 or anti-CD11b and anti-CD11c MAbs to cause a marked increase in nitrite-oxidative products and pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF alpha). These CD23-mediated activities were decreased by Fab fragments of MAbs to CD11b, CD11c, and CD23. These results demonstrate that CD11b and CD11c are receptors for CD23 and that this novel ligand pairing regulates important activities of monocytes.
Lecoanet-Henchoz
S
S
Glaxo Institute for Molecular Biology, Geneva, Switzerland.
Gauchat
J F
JF
Aubry
J P
JP
Graber
P
P
Life
P
P
Paul-Eugene
N
N
Ferrua
B
B
Corbi
A L
AL
Dugas
B
B
Plater-Zyberk
C
C
D018845:CD11 Antigens / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008081:Liposomes; D009000:Monocytes / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction
D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D008081:Liposomes; D017455:Receptors, IgE; D006861:Hydrogen Peroxide