MRL/lpr and MRL+/+ macrophage DNA synthesis in the absence and the presence of colony-stimulating factor-1 and granulocyte-macrophage colony-stimulating factor

Macrophage accumulation and proliferation as well as altered macrophage pro perties have been observed in autoimmune MRL mice, To determine whether the re might be innate differences in the proliferative responses, we examined the DNA synthesis responses of peritoneal macrophages and macrophages deriv ed in vitro from bone marrow precursors (bone marrow-derived macrophages (B MM)), Murine peritoneal exudate macrophages normally require the addition o f macrophage CSF (CSF-1) to enter cell cycle in vitro. In contrast, we have found that many thioglycollate-induced adherent peritoneal macrophages, bu t not resident peritoneal macrophages, from both MRL/lpr and MRL+/+ mice at ypically underwent DNA synthesis even in the absence of added CSF-1. They a lso responded very well to granulocyte-macrophage CSF, These findings may h elp to explain the appearance of increased macrophage numbers in MRL lesion s. In contrast to a previous report, it was found that MRL/lpr and MRL+/+ B MM did not have an enhanced response to CSF-1 and that modulation of CSF-1 receptor expression was not more rapid in MRL BMM, We also found no evidenc e for abnormal CSF-1 internalization and degradation or for the lpr mutatio n to have any enhanced effect on BMM survival in the absence of CSF-1. TNF- alpha lowered the DNA synthesis response to CSF-1 of MRL/lpr BMM rather tha n enhanced it, as has been reported. Our data suggest that the enhanced acc umulation of macrophages in the MRL/lpr kidney cannot be explained by a pro posed model of enhanced responsiveness of MRL/lpr BMM to CSF-I, including a contribution by TNF-alpha.