Induction of mouse monocyte Ia expression by a mesangial cell-derived product

Previous studies in many laboratories have shown that macrophage Ia expression is not constitutive but under regulation. We provide data which demonstrate that product(s) of mouse mesangial cell cultures induce blood monocyte Ia expression as demonstrated by immunofluorescence. This process is time-related and is also dependent on novel protein synthesis, being abrogated when the monocytes are pretreated with cycloheximide. Preliminary characterization shows the mesangial cell product to be sensitive to heating at 100 degrees C x 30 min, to be resistant to digestion by trypsin at a concentration of 4 x 10(-6) M, and to have a molecular size of 10-100 kD as established by Amicon ultrafiltration. The substance is not interferon-gamma (IFN-gamma) since cultured mesangial cells had no contaminating T cells, mesangial cell supernatant had no detectable levels of IFN-gamma, and the Ia-inducing activity of the mesangial cell product was not abrogated by incubation of monocytes with mesangial cell supernatant which had been immunoprecipitated with anti-IFN-gamma. Similarly, experiments using anti-CSF-1 have excluded the possibility that the substance is CSF-1. The results of the study have relevance to the mechanisms by which monocytes which take up residence in the glomerular mesangium acquire Ia positivity, and also provide a potentially novel pathway by which a tissue product may induce monocytes to express Ia.