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

SUMMARY Previous studies in many laboratories have shown that macrophage hi expression is not constitutive but under regulation. We provide data which demonstrate that product(s) of mouse mesangial cell cultures Induce blood monocyte la expression as demonstrated by immunofluoresconce. This process is time-reialed and is also dependent on novel protein synthesis, being abrogated when themonocytes arepretreated with cycloheximidc. Preliminary characterization shows the mesangial cell product to be sensitive to healing at 100°C × 30 min, to be resistant to digestion by trypsin at a concentration of 4 × 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-γ) since cultured mesangial cells had no contaminating T cells, mesangial cell supernatant had no delectable levels of IFN-γ, and the Ia-inducing activity of the mesangial cell product was not abrogated by incubation of monoeytes with mesangial cell supernatant which had been immunoprecipitated with anti-IFN-γ. 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 inonocytes which take up residence in the glomerular mesangium acquire la positivity. and also provide a potentially novel pathway by which a tissue product may induce monocytes to express Ia.