Angiotensin II augmentation of tyrosine kinase activity in human adherent mononuclear cells.

The relationship of angiotensin converting enzyme activity and angiotensin II to the inflammatory process in diseases such as sarcoidosis remains unclear. We hypothesize that granuloma macrophages regulate inflammation by release of angiotensin converting enzyme, which produces angiotensin II, and that angiotensin II in turn modulates monocyte/macrophage activity. Since tyrosine kinase catalyzes phosphorylation of tyrosine residues in proteins and is important in signal transduction and cellular activation, we further postulated that monocyte tyrosine kinases may play a role in the regulation of this process. Mononuclear cells from 11 healthy subjects were assayed for tyrosine kinase activity in the presence and absence of angiotensin II. In addition, tyrosine-specific phosphorylation of cellular proteins was also determined. Angiotensin II increased tyrosine kinase activity in a concentration-dependent manner. The maximal stimulation, which varied from 31 to 506%, was achieved following incubation of cells with 10(-4) M angiotensin II. Angiotensin II also increased the tyrosyl-phosphorylation of three proteins with molecular weights of 57, 62, and 63 kDa. We conclude that tyrosine kinase activity of adherent mononuclear cells and tyrosine phosphorylation of certain protein(s) may be involved in angiotensin II regulation of inflammatory processes.