EPITHELIOID CELLS FROM FOREIGN-BODY GRANULOMA SELECTIVELY EXPRESS THECALCIUM-BINDING PROTEIN MRP-14, A NOVEL DOWN-REGULATORY MOLECULE OF MACROPHAGE ACTIVATION

The S-100 proteins MRP-8 and MRP-14 are expressed by cells of the myel omonocytic lineage, either alone or simultaneously during-cer lain sta ges of cellular differentiation. We demonstrate that MRP-14 but not MR P-8 was detected by immunostaining in the cytoplasm of epithelioid cel ls on the surface of round coverslips implanted for 14 days into the s ubcutaneous tissue of mice. Using this experimental model, our laborat ory has previously shown that epithelioid macrophages are poor phagocy tic cells that release a macrophage-deactivating factor (MDF) in short -term cultures, The full chemical characterization of MDF has not been achieved so far. We provide evidence that the calcium-binding protein MRP-14 was also released by epithelioid macrophages in short-term cul tures and that its neutralization from the culture medium after additi on of monoclonal antibody anti-MRP-14 abolished the MDF activity of ti le conditioned medium, Purified or recombinant human MRP-14 but not MR P-8 inhibits the respiratory burst of BCG-activated macrophages. Recom binant mouse MRP-14 also down-regulate macrophage activation in vitro, and PMA does not revert the inhibitory effect induced by MRP-14. It i s thus concluded that epithelioid cells from foreign-body granuloma ex press and release MRP-14 in short-term cultures and that this molecule is endowed with MDF activity.