Substance P induces chemotaxis of neutrophils in normal and capsaicin‐treated rats

Abstract

Summary. Primary afferent iinmyetinated nerves modulate ihe intlammatory response to injury through a process known as neurogenic inflammation. The undecapeptide Substance P is contained in many of these nerves and therefore may be an important mediator of the response. Treatment of neonatal rats with capsaicin permanently destroys primary afferent unmyelinated nerves and depletes (he skin and other organs of Substance P. These animals have a reduced capacity to mount an inflammatory response to injury. We examined the ability of Substance P to chemo-attract neutrophils from normal rats and rats treated a.s neonates with capsaicin. Substance P was shown to cause normal rat neutrophils to chemotact at an optimum concentration of 5 x 10 -' ' M. Equivalent chemotaxis was observed in neutrophils from rats pretreated as neonates with capsaicin. Substance P did not increase chemokinesis. These in vitro results support the view that the reduced neurogenic inflammatory response seen in capsaicin-pretreated rats is not due to a direct toxic effect of capsaicin on neutrophils, but may be due to a decreased availability of neurally derived Substance P a£ the site of injury.

Neutrophil Recruitment by Interleukin-17 into Rat Airways In Vivo

“…In rat airways, SP potently increases adhesion and transvascular migration of neutrophils (24). SP also induces neutrophil chemotaxis both in vivo (36) and in vitro for human (37) and rat (38) cells, respectively. In addition, a NK-1 receptor antagonist reduces the number of neutrophils in airways after allergen challenge in sensitized mice (39).…”

The Role of Neuromediators and Innervation in Cutaneous Wound Healing

“…SP stimulates vasodilatation and micro-vascular permeability through increasing nitric oxide release and through direct effects on endothelial cells (32). SP up-regulates expression of adhesion molecules on endothelial cells, monocyte chemotaxis and inflammatory cell activity (33)(34)(35). SP also modulates the synthesis and release of pro-inflammatory cytokines such as interleukins, transforming growth factor-α (TGF-α) and tumour necrosis factor-α; key components during the inflammatory phase of wound healing (36).…”

Effect of partial transection of spinal cord on permeability of cutaneous vessels in rats before and after treatment with neurotoxic dose of capsaicin

“…Ulceration of the skin was accompanied by increased dye accumulation (22.0+8.1 ~tg/mg tissue, p<0.05). This increase was probably caused by primary release of vasoactive neuropeptides from capsaicinsensitive terminals followed by depletion of peptide stores in CNS, because the primary stages of neurogenic inflammation are characterized by enhanced release of tachykinins (substance P [3]), while weakening of the neural control results in deficiency of skin homeostasis and can provoke delayed hypersensitivity reaction [5].…”