Substance P-induced @entity32 responses in XXXX skin: the effect of specific @entity13630 antagonists and the role of endogenous mediators.

@entity17567 @entity32 @entity10133 @entity48741 @entity13630 @entity4 @entity840 @entity73255 @entity112 @entity71362 @entity10126 @entity13624
1. The sensory neuropeptide substance @entity10133 ), when released from sensory nerves, has been implicated in the development of @entity13624 . In the present study, using an in vivo model system, we have characterized and investigated the mechanisms underlying SP-induced leukocyte accumulation and @entity4 formation in the @entity840 . 2. Intradermally injected SP (i.d., 10(-13) - 10(-9) mol per site), induced a dose- and time-dependent accumulation of 111In-neutrophils, 111In-eosinophils and @entity4 formation as measured by the local accumulation of i.v. injected 125I-albumin. The leukocyte accumulation evoked by SP was significant at 10(-10) and 10(-9) mol per site, whereas @entity4 formation was significant at the lowest dose tested (10(-13) mol per site). 3. The @entity13630 antagonists, @entity48741 (1 mg kg-1, i.v.) and @entity10126 (10 micrograms per site, i.d.), significantly attenuated the @entity4 formation induced by the lower doses of SP. @entity4 formation and leukocyte accumulation induced by 10(-9) mol per site SP were unaffected by either antagonist. 4. SP-elicited responses were not significantly affected by the @entity71362 antagonist, UK-74,505 (2.5 mg kg-1, i.v.) or the H1 @entity112 receptor antagonist, @entity17567 (10(-8) mol per site, i.d.). However, the 111In-eosinophil accumulation, but not the 111In-neutrophil accumulation or @entity4 formation, induced by SP was significantly inhibited by the specific 5-lipoxygenase (5-LO) inhibitor, @entity73255 (10(-8) mol per site, i.d.). 5. The accumulation of both 111 In-neutrophils and 111 In-eosinophils induced by SP was abolished in @entity840 treated i.v. with an anti-CD18 monoclonal antibody 6.5E F(ab')2 (2.5 mg kg-1). The @entity4 response was unaffected in these animals.6. These results suggest that SP-induced @entity32 events may be mediated via two mechanisms involving @entity13630 -dependent and independent pathways. @entity4 formation induced by the lower doses of SP may be mediated via the direct activation of NK1 receptors whilst, at higher doses, @entity4 formation and leukocyte accumulation may be mediated via the release of secondary mediators, possibly mast cell derived, with 5-LO products playing an important role in the leukocyte infiltration. The leukocyte accumulation, but not the @entity4 induced by SP, is dependent on the expression of the CD18antigen on leukocytes.
