Synthetic inotropes inhibit the expression of adhesion molecules and augment the expression of l-selectin in polymorphonuclear neutrophils

Abstract

To elucidate differential functional and phenotypic changes in response to clinically relevant synthetic inotropes plus the generation of oxidative free radicals by polymorphonuclear neutrophils (PMN), and changes in the expression of L-selectin and Mac-1 on the surface of PMN were examined in the presence of dobutamine and dopexamine in pharmacological concentrations. Prospective, in vitro study. Research laboratory. Human PMN obtained from healthy donors. PMN were pretreated with dobutamine 147.99 nM or 147,990 nM, or dopexamine 100 nM or 100,000 nM, followed by stimulation with FMLP. Stimulated neutrophils were incubated with antibiodies against CD11b or CD62l and assessed by flow cytometry. Additional probes were assessed by flow cytometry for the generation of oxidative free radicals. Low concentrations of both synthetic inotropes significantly inhibit the suppression of CD62l expression following stimulation with N-formyl-l-methionyl-l-leucyl-l-phenylalanine; high concentrations antagonize this effect. High concentrations of both synthetic inotropes suppresses the expression of CD11b. Neither dobutamine nor dopexamine modified the generation of oxidative free radicals. While the upregulation of Mac-1 expression is inhibited in a dose-dependent manner, the expression of L-selectin is enhanced at low concentrations of dobutamine and dopexamine and partly counter-regulated at high concentrations. It seems that synthetic inotropes can modulate the immunomodulatory ability by inhibition of PMN rolling and modification of PMN adherence and diapedese.