Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated protein kinase and chemotaxis in human neutrophils

Abstract

Propofol is used in the peri-operative setting and may affect some neutrophil functions. The effects of propofol on the function and intracellular signal transduction systems of neutrophils is controversial. Mitogen-activated protein kinase families (MAPKs) are members of the intracellular signal-transducing systems in eukaryotes. MAPKs have been shown to be involved in neutrophil chemotaxis by the use of PD98059, the specific inhibitor of MAPK/ERK kinase (MEK). The effects of propofol in dimethyl sulfoxide on phosphorylation of MAPKs and chemotaxis were investigated in human neutrophils. Isolated neutrophils (2 x 10(7) cells per ml) from healthy volunteers were incubated with propofol (2-500 microM) and stimulated by N-formyl-L-methionyl-phenylalanine (FMLP) (100 nM). The effects of propofol on the phosphorylation of p44/42 MAPK were investigated by immunoblotting. The effects of FMLP (1 microM) on chemotaxis were investigated with the under-agarose method. The phosphorylation of p42 MAPK and chemotaxis stimulated by FMLP were both inhibited by propofol at clinically relevant concentrations (> or = 10 and > or = 20 microM respectively). PD98059 (50 microM) also inhibited chemotaxis stimulated by FMLP, suggesting the involvement of p42 MAPK in the response. Propofol might therefore inhibit human neutrophil chemotaxis, at least in part, by suppressing the p44/42 MAPK pathway.