MOUSE CD23 REGULATES MONOCYTE ACTIVATION THROUGH AN INTERACTION WITH THE ADHESION MOLECULE CD11B CD18/

CD23 is expressed on a variety of hemopoietic sells, Recently, we have reported that blocking CD23 interactions in a murine model of arthrit is resulted in a marked improvement of disease severity. Here, we demo nstrate that CD11b, the a chain of the beta(2) integrin adhesion molec ule complex CD11b/CD18 expressed on monocytes interacts with CD23. Usi ng a recombinant fusion protein (ZZ-CD23), murine CD23 was shown to bi nd 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 significan tly inhibited by anti-CD11b monoclonal antibodies. A functional conseq uence was then demonstrated by inducing an up-regulation of interleuki n-6 (IL-6) production following ZZ-CD23 incubation with monocytes. The addition of Fab fragments generated from the monoclonal antibody CD11 b impaired this cytokine production by 50%. Interestingly, a positive autocrine loop was identified as IL-6 was shown to increase CD23 bindi ng 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 activites of murine myeloid cells.