Tachykinins: Effects on Motility and Metabolism of Rat Polymorphonuclear Leucocytes

Abstract

Chemotactic and chemoluminescent activities of substance P, substance K, kassinin and the substance P fragments SP 4-11, SP 7-11, SP 1-4 have been investigated in order to identify the minimum active molecular structure responsible for rat polymorphonuclear activation. Substance P, SP 4-11 and SP 7-11 stimulated directed locomotion (chemotaxis) and were found to be active also in the chemoluminescence assay while SP 1-4 had no effect. Moreover, all peptides, except substance K and SP 1-4, inhibited the chemotactic response of polymorphonuclears to the peptide formylmethionyl-leucyl-phenylalanine and, to a minor extent, also to leukotriene B₄. A maximum of activity was observed with the C-terminal sequence SP 4-11. Substance K was found to be inactive. Kassinin exhibited a weak chemotactic effect and exerted a slight inhibition of attracting activity of peptide-formyl-methionyl-leucyl-phenylalanine. Considering that substance P and related peptides are active only at very high concentrations, it cannot be affirmed that these agents activate specific receptors. If receptors are involved, they would be of the SP-P type, since substance K is inactive.

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

“…Similar to our results with SR140333, neutrophil recruitment was not affected in a model of thermal injury in rats (48). Roch-Arveiller and colleagues examined the response of rat neutrophils to substance P and found concentration-dependent chemotaxis only at high concentrations (10 26 -10 24 mol/liter) (49).…”

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

“…Similar to our results with SR140333, neutrophil recruitment was not affected in a model of thermal injury in rats (48). Roch-Arveiller and colleagues examined the response of rat neutrophils to substance P and found concentration-dependent chemotaxis only at high concentrations (10 26 -10 24 mol/liter) (49).…”

Neutral endopeptidase modulates neurogenic inflammation

“…Only after treatment with phosphoramidon did significant chemotaxis occur, and even under these conditions, chemotaxis was only mild [56). These results are compatible with the reports that substance P is only very weakly chemotactic for neutrophils in vitro [59][60][61]. Both neutrophils [62) and tracheal postcapillary venules (Nadel, Ueki and Piedimonte, personal observation) contain NEP; their individual contribution to neutrophil adhesion is unknown.…”

Topical substance P increases inflammatory cell density in genetically diabetic murine wounds

“…Temporally, this proinflammatory effect corresponds with known sequences of inflammatory cell migration in healing wounds, with leukocytes marginating into tissue first followed by macrophages. Because SP-induced migration of in vitro inflammatory cells has been documented [13][14][15] and SP has been shown to up-regulate interleukin-8 (IL-8) in several cell types, 6 our data suggest that SP effects on wound healing kinetics may relate to its ability to increase early inflammation. It is not clear whether SP-induced inflammatory cell recruitment is due to its ability to increase capillary permeability 4 and up-regulation of endothelial cell adhesion molecules 27 or to direct chemoattractant effect on the inflammatory cells themselves.…”

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

“…Similar to our results with SR140333, neutrophil recruitment was not affected in a model of thermal injury in rats (48). Roch-Arveiller and colleagues examined the response of rat neutrophils to substance P and found concentration-dependent chemotaxis only at high concentrations (10 26 -10 24 mol/liter) (49).…”

Neutral endopeptidase modulates neurogenic inflammation

“…Only after treatment with phosphoramidon did significant chemotaxis occur, and even under these conditions, chemotaxis was only mild [56). These results are compatible with the reports that substance P is only very weakly chemotactic for neutrophils in vitro [59][60][61]. Both neutrophils [62) and tracheal postcapillary venules (Nadel, Ueki and Piedimonte, personal observation) contain NEP; their individual contribution to neutrophil adhesion is unknown.…”

Topical substance P increases inflammatory cell density in genetically diabetic murine wounds

“…Temporally, this proinflammatory effect corresponds with known sequences of inflammatory cell migration in healing wounds, with leukocytes marginating into tissue first followed by macrophages. Because SP-induced migration of in vitro inflammatory cells has been documented [13][14][15] and SP has been shown to up-regulate interleukin-8 (IL-8) in several cell types, 6 our data suggest that SP effects on wound healing kinetics may relate to its ability to increase early inflammation. It is not clear whether SP-induced inflammatory cell recruitment is due to its ability to increase capillary permeability 4 and up-regulation of endothelial cell adhesion molecules 27 or to direct chemoattractant effect on the inflammatory cells themselves.…”

Activation of Neurokinin-1 Receptors during Ozone Inhalation Contributes to Epithelial Injury and Repair

“…Similar to our results with SR140333, neutrophil recruitment was not affected in a model of thermal injury in rats (48). Roch-Arveiller and colleagues examined the response of rat neutrophils to substance P and found concentration-dependent chemotaxis only at high concentrations (10 26 -10 24 mol/liter) (49).…”

Neutral endopeptidase modulates neurogenic inflammation

“…Only after treatment with phosphoramidon did significant chemotaxis occur, and even under these conditions, chemotaxis was only mild [56). These results are compatible with the reports that substance P is only very weakly chemotactic for neutrophils in vitro [59][60][61]. Both neutrophils [62) and tracheal postcapillary venules (Nadel, Ueki and Piedimonte, personal observation) contain NEP; their individual contribution to neutrophil adhesion is unknown.…”

Topical substance P increases inflammatory cell density in genetically diabetic murine wounds

“…Temporally, this proinflammatory effect corresponds with known sequences of inflammatory cell migration in healing wounds, with leukocytes marginating into tissue first followed by macrophages. Because SP-induced migration of in vitro inflammatory cells has been documented [13][14][15] and SP has been shown to up-regulate interleukin-8 (IL-8) in several cell types, 6 our data suggest that SP effects on wound healing kinetics may relate to its ability to increase early inflammation. It is not clear whether SP-induced inflammatory cell recruitment is due to its ability to increase capillary permeability 4 and up-regulation of endothelial cell adhesion molecules 27 or to direct chemoattractant effect on the inflammatory cells themselves.…”