Priming effects of substance P on calcium changes evoked by interleukin-8 in human neutrophils

The neurokinin (NK) substance P (SP), which is a mediator of neurogenic inflammation, has been reported to prime human polymorphonu- clear neutrophils (PMNs). The priming effects of SP on PMNs activated by recombinant interleu- kin-8 (rIL-8) were investigated. SP enhanced, in a dose- and time-dependent way, the rise in cytosolic free-calcium concentration, (Ca 21 )i, evoked by the chemokine. The priming effects of SP were abol- ished by exposing PMNs to a calcium-free medium supplemented with EGTA. The C-terminal peptides SP(4-11) and SP(6-11) but not the N-terminal peptide SP(1-7) shared the priming effects of SP. The selective NK-1 receptor agonist (Sar-9, Met(O) 2-11)SP mimicked the effects of SP, which were not reproduced by the selective NK-2 recep- tor agonist (bAla-8)-NKA(4-10) or the selective NK-3 agonist senktide. Two selective NK-1 antago- nists, CP96,345 and L703,606, dose dependently inhibited SP priming effects. These results demon- strated that SP primes PMNs exposed to rIL-8 and suggested that SP priming effects are receptor mediated. J. Leukoc. Biol. 69: 1013-1018; 2001.