IN MONOCYTES Results

Transglutaminases are a group of enzymes that catalyze the covalent conjugation of amines to protein-bound glutamine residues. The products of transglutaminase activity are proteins covalently cross-linked by ~-(3"-glutaminyl)-lysine isopeptide bonds and proteins containing covalently conjugated polyamines (16). Several distinct intracellular and extracellular transglutaminases have been identified (1, 2). The predominant form of this enzyme in liver and cultured fibroblasts is tissue transglutaminase, an ~80,000 D polypeptide (2, 7-9). We have measured the amounts of this enzyme in a variety of normal and transformed cell types and have found that macrophages can contain extremely high levels (9). Studies from several laboratories have indicated that transglutaminase may play an important role in macrophage function. Activation of guinea pig and mouse macrophages in vivo is associated with marked increases in transglutaminase activity due to a dramatic induction of tissue transglutaminase (9-11). In both cell types, elevated levels of transglutaminase activity have been correlated with enhanced Fc receptor-mediated phagocytic capacity (10-12). Furthermore, several inhibitors of transglutaminase activity block phagocytosis of immune complexes and opsonized erythrocytes (1 1, 12). However, the precise role of transglutaminase in macrophage function remains to be determined. Peripheral blood monocytes can differentiate into macrophages when cultured in vitro (13-18). The differentiation of myelobastic cells into macrophages has been associated with marked increases in the levels of transglutaminase (10, 19). Therefore, we were interested in determining the level of tissue transglutaminase in peripheral blood monocytes and if differentiation of these cells into macrophages was associated with alterations in the level of the enzyme. We report here that the levels of tissue transglutaminase in freshly isolated human peripheral blood monocytes are very low but that the enzyme accumulates to significant levels during culture of these cells in vitro. This work was supported in part by grant AM27078 from the National Institutes of Health, grant BC334A from the American Cancer Society, and by a grant from the Kroc Foundation. * To whom correspondence should be addressed at the Department of Pharmacology, University of Texas Medical School, P.O. Box 20708, Houston, TX 77025. * Current address is the Division of Rheumatology, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262.