Mouse CD23 regulates monocyte activation through an interaction with the adhesion molecule CD11b/CD18.
CD23 is expressed on a variety of hemopoietic cells. Recently, we have reported that blocking CD23 interactions in a murine model of arthritis resulted in a marked improvement of disease severity. Here, we demonstrate that CD11b, the alpha chain of the beta 2 integrin adhesion molecule complex CD11b/CD18 expressed on monocytes interacts with CD23. Using a recombinant fusion protein (ZZ-CD23), murine CD23 was shown to bind to peritoneal macrophages and peripheral blood cells isolated from mice as well as the murine macrophage cell line, RAW. The interactions between mouse ZZ-CD23 and CD11b/CD18-expressing cells were significantly inhibited by anti-CD11b monoclonal antibodies. A functional consequence was then demonstrated by inducing an up-regulation of interleukin-6 (IL-6) production following ZZ-CD23 incubation with monocytes. The addition of Fab fragments generated from the monoclonal antibody CD11b impaired this cytokine production by 50%. Interestingly, a positive autocrine loop was identified as IL-6 was shown to increase CD23 binding to macrophages. These results demonstrate that similar to findings using human cells, murine CD23 binds to the surface adhesion molecule, CD11b, and these interactions regulate biological activities of murine myeloid cells.
Lecoanet-Henchoz
S
S
Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, Switzerland.
Plater-Zyberk
C
C
Graber
P
P
Gretener
D
D
Aubry
J P
JP
Conrad
D H
DH
Bonnefoy
J Y
JY
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology*; D002460:Cell Line; D015850:Interleukin-6 / Q000096:biosynthesis; D008262:Macrophage Activation; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D011108:Polymers; D017455:Receptors, IgE / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction
D018821:CD18 Antigens; D015850:Interleukin-6; D016177:Macrophage-1 Antigen; D011108:Polymers; D017455:Receptors, IgE; D011993:Recombinant Fusion Proteins