| Popis: |
This study examines the contribution of tachykinins to the processes of inflammation. Neurokinin A (NKA), neurokinin B (NKB) and eledoisin (E) but not kassinin (K) have similar effects to substance P (SP) in priming neutrophils for increased superoxide anion (O2-) production in response to formyl-methionyl-leucyl-phenylalanine (FMLP). This similarity in activity may be due to the carboxy amino acid terminal end of these tachykinins being highly conserved. This was confirmed by demonstrating that SP fragment 7-11 (SP7-11) had the same priming effect as the whole molecule, whereas, the amino end fragment 1-4 (SP1-4) inhibited the response to FMLP. The priming effect of tachykinins was not confined to a single stimulus, such as FMLP, since NKA, NKB and SP also enhanced O2- production stimulated by platelet-activating factor (PAF), an important mediator of inflammation but a weak stimulus of O2- production on its own. In addition, all the tachykinins studied increased neutrophil antibody-dependent cell-mediated cytotoxicity (ADCC) towards opsonized target cells. In contrast to their effects on FMLP-induced O2- production, both SP fragments, SP1-4 and SP7-11, stimulated neutrophil ADCC and had a synergistic effect when used together. |
