Trp-Lys-Tyr-Met-Val-D-Met is a chemoattractant for human phagocytic cells

Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) is a synthetic peptide that stimulates p hosphoinositide (PI) hydrolysis in human leukocytes. The peptide binds to a unique cell surface receptor(s), Recently we had demonstrated that hunan n eutrophils, monocytes, and B lymphocytes express this peptide-specific rece ptor and that stimulation of human leukocytes with the peptide leads to act ivation of the oxidative respiratory system and the bactericidal activity o f neutrophils or monocytes. In this study we showed that the peptide induce s chemotaxis of phagocytic leukocytes and studied the signaling pathway lea ding to chemotaxis in human monocytes. The peptide-induced monocyte chemota xis is pertussis toxin (PTX)-sensitive. This fact correlates with the pepti de's stimulation of PI hydrolysis and intracellular Ca2+ ([Ca2+](i)) releas e, which is also PTS-sensitive. We demonstrate that the peptide-specific re ceptor is different from receptor(s) for monocyte chemoattractant protein-1 (MCP-1). We also show that intracellular signaling of WKYMVm leading to mo nocyte chemotaxis is different from that of MCP-1, The peptide-mediated mon ocyte chemotaxis is insensitive to protein kinase C (PKC) inhibitor (GF1092 03X) and butan-1-ol, 1-ol, ruling out PKC and phospholipase D participation in this process. On the other hand, a tyrosine kinase inhibitor (genistein ) and RhoA inhibitor (C3 transferase) curtailed the peptide-induced chemota xis in a concentration-dependent mariner, implying the involvement of tyros ine kinase and RhoA, respectively. Treatment of human monocytes with the pe ptide stimulates tyrosine phosphorylation of several cellular proteins, inc luding p125FAK and Pyk2 and translocation of RhoA from the cytosol to the m embrane. We conclude that WKYMVm induces chemotaxis of human phagocytic leu kocytes via unique receptors and signaling.