Characterization of extracellular nucleotide-induced Mac-1 (alphaM beta2 integrin) surface expression on peripheral...

Extracellular nucleotides, released during vascular injury, stimulate hematopoietic cells resulting in various physiological responses. We have determined that nucleotides can stimulate the expression of Mac-1 on peripheral blood leukocytes. ATP stimulated the expression of Mac-1 in a time- and dose-dependent manner with maximum expression occurring in 5 min at 10 microM ATP. This increase in surface expression was observed in monocytes and granulocytes was dose-dependent and was comparable in extent to the increase induced by the chemotactic peptide, formyl-Met-Leu-Phe. Other nucleotides including 2-MeSADP, ADP, UTP, and 2MeSATP had similar effect. Nucleotide-mediated stimulation of Mac-1 expression in granulocytes was completely inhibited by Ro-31-8220, a specific inhibitor of protein kinase C, while variable inhibition was observed in monocytes. These results demonstrate the stimulation of peripheral blood leukocytes by nucleotides causing an increased surface expression of Mac-1 which may be mediated by the activation of protein kinase C.