We have previously investigated the regulation of M-CSF production from human monocytes induced by various cytokines. The results of these studies have been published. We have expanded this work and have examined the ability of antibodies to the surface antigens: CD45, CD44 and LFA-3 to stimulate M-CSF production. Immobilized antibodies to all three antigens were able to induce M-CSF mRNA while antibodies to other surface proteins did not. F(ab)2 fragments of a CD45 antibody were used to demonstrate that this process did not require Fc binding. Although these same antibodies also induced some measurable M-CSF release, second signals provided by LPS or IL-1beta greatly augmented the M-CSF production when added to the cultures. LPS or IL-1beta alone were not able to stimulate M-CSF protein release. These results have been published. We are currently investigating the molecular mechanisms involved in the induction of M-CSF message in human monocytes costimulated with CD45 and IL-1beta. Preliminary data suggest that for the IL-lbeta-induced enhancement of M-CSF message of CD45 stimulated monocytes, both transcriptional and posttranscriptional mechanisms are required. M-CSF message induced by these stimuli is not blocked by CHX, indicating that protein synthesis is not required. In addition, we have initiated studies to investigate the role of CD45 in c-fms expression.
