COMPLEXITY IN UTERINE MACROPHAGE RESPONSES TO CYTOKINES IN MICE

Uterine stromal macrophages change dramatically in density and morphol ogy through the estrous cycle and during early pregnancy, whereas thos e in the mesometrial triangle do not undergo these changes. The mononu clear phagocytic growth factor, colony-stimulating factor-1 (CSF-1), r egulates both the density and morphology of uterine macrophage populat ions, as shown by the fact that uterine macrophages are depleted and m ore rounded in the absence of CSF-1 caused by the osteopetrotic (csfm( op)) null mutation, compared to those of normal mice. Restoration of c irculating CSF-1 to the nullizygous mice did not affect stromal macrop hage density although it restored the population in the mesometrial tr iangle. This suggests CSF-1 regulation of these macrophage populations by local and humoral routes, respectively. Nevertheless, even in the absence of CSF-1, stromal macrophage population density varies 30-fold through the estrous cycle, suggesting the involvement in their regula tion of factors other than CSF-1, such as the chemokines, which are ch emoattractive for macrophages. The mRNA for the chemokines JE (MCP-1), C10, RANTES, and MIP1 alpha are expressed in the uterus, with elevate d levels observed on the first day of pregnancy. Such molecules, toget her with CSF-1, may play a role in modulating the complexities of uter ine macrophage dynamics in response to sex steroid hormones and mating .