Priming of normal human neutrophils by tachykinins: tuftsin-like inhibition of in vitro chemotaxis stimulated by formylpeptide or interleukin-8.
Tachykinins have priming effects on polymorphonuclear neutrophils, since they may activate the neutrophils to exhibit an exaggerated inflammatory response to phlogistic mediators. In order to investigate mechanisms involved in this action, we determined the influence of substance P and neurokinin A on chemotaxis of human neutrophils towards gradients of formymethionyl-leucyl-phenylalanine or recombinant human interleukin-8. As seen with other neutrophil-priming agents such as tumor necrosis factor-alpha, exposure of neutrophils to substance P or neurokinin A had an inhibitory effect upon a stimulated migration, with effective concentrations being in the nanomolar range. Tuftsin, a known neutrophil activating peptide, similarly inhibited stimulated migration. Analysis of structure-activity relationships revealed that activity of tachykinins is located in amino-terminal, tuftsin-like sequences. The inhibition of stimulated migration was partly reversed by (Pro1)-tuftsin, a partial tuftsin receptor antagonist, which suggests that the effects of amino-terminal tachykinins involves activation of tuftsin receptors of neutrophils.
Wiedermann
C J
CJ
Department of Internal Medicine, Faculty of Medicine, University of Innsbruck, Austria.
Niedermühlbichler
M
M
Zilian
U
U
Geissler
D
D
Lindley
I
I
Braunsteiner
H
H
D000595:Amino Acid Sequence; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects*; D015320:Tachykinins / Q000494:pharmacology*; D014405:Tuftsin / Q000494:pharmacology*
D002630:Chemotactic Factors; D016209:Interleukin-8; D015320:Tachykinins; D014405:Tuftsin