The interaction of particulates with resident macrophages is a consistent feature in certain forms of crystal-induced
inflammation, for example, in synovial tissues, lung, and the peritoneum. The mitogenic activity of basic
calcium phosphate (BCP) crystals and
calcium pyrophosphate dihydrate (CPPD) crystals on synovial fibroblasts has been considered relevant to the synovial
hyperplasia observed in crystal-induced
arthritis. The aim of the study was to determine whether microcrystals such as these could enhance macrophage survival and induce
DNA synthesis, thus indicating that they may contribute to the tissue
hyperplasia. Murine bone-marrow-derived macrophages were treated in vitro with microcrystals, the cell numbers were monitored over time, and
DNA synthesis was measured as the incorporation of [methyl-(3)H]
thymidine (TdR). We report here that BCP,
monosodium urate,
talc, and, to a lesser extent, CPPD crystals promote macrophage survival and
DNA synthesis; the latter response is particularly striking in the presence of low concentrations of
macrophage-colony stimulating factor (M-CSF, CSF-1). Enhanced macrophage survival or proliferation may contribute to the synovial
hyperplasia noted in crystal-associated
arthropathies, as well as to
talc-induced
inflammation and
granuloma formation. The crystals studied join the list of particulates having these effects on macrophages, indicating the generality of this type of response.