title: Activation of human neutrophils by tachykinins: effect on formyl-methionyl-leucyl-phenylalanine- and platelet-activating factor-stimulated superoxide anion production and antibody-dependent cell-mediated cytotoxicity.
abstract: 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.
authors.affiliation: Department of Thoracic Medicine, Royal Adelaide Hospital, South Australia.
authors.forename: A
authors.initials: A
authors.lastname: Wozniak
authors.forename: W H
authors.initials: WH
authors.lastname: Betts
authors.forename: G
authors.initials: G
authors.lastname: McLennan
authors.forename: R
authors.initials: R
authors.lastname: Scicchitano
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000276:immunology; D013373:Substance P / Q000276:immunology; D013481:Superoxides / Q000378:metabolism*; D015320:Tachykinins / Q000276:immunology*
chemical_list: D010972:Platelet Activating Factor; D015320:Tachykinins; D013481:Superoxides; D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine