Neurogenic inflammation of the rat trachea: fate of neutrophils that adhere to venules

Abstract

The goal of this study was to determine whether neutrophils that adhere to the vascular endothelium in association with neurogenic inflammation in the respiratory tract migrate out of the blood vessels or whether they detach and reenter the circulation. We also sought to determine whether the fate of the neutrophils is influenced by neutral endopeptidase (NEP), an enzyme that degrades the tachykinins that produce neurogenic inflammation. Neutrophils in the tracheal mucosa of anesthetized pathogen-free rats were examined 5 min or 4 h after neurogenic inflammation was produced by an injection of capsaicin (100 or 200 micrograms/kg iv). In whole mounts of these tracheae stained histochemically for myeloperoxidase, adherent intravascular neutrophils had a spherical or teardrop (regular) shape and migrating neutrophils had a polarized amoeboid (irregular) shape. The number of regular neutrophils in the tracheae was increased at both times, but the increase at 4 h was only half that present at 5 min. The reduction between 5 min and 4 h was not offset by an appreciable increase in the number of irregular neutrophils, unless NEP was inhibited by phosphoramidon. We interpret these results as indicating that the rapid adherence of neutrophils to the vascular endothelium after an injection of capsaicin is followed by a gradual reentry of the neutrophils into the circulation and comparatively little neutrophil migration. However, when the effect of the stimulus is increased and/or prolonged by inhibition of NEP, some of the adherent neutrophils migrate out of the vessels. Thus the activity of NEP can regulate both the magnitude of the neutrophil adherence and the fate of the adherent cells.

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

“…The cell-surface enzyme neutral endopeptidase (NEP) degrades SP in the extracellular fluid and may thereby terminate its proinflammatory effects (11,12). Administration of NEP inhibitors potentiates neurogenic inflammation in the airway by preventing the degradation of SP (13,14). Genetic deletion of NEP leads to markedly elevated plasma extravasation in the small intestine that is prevented by administration of an NK1R antagonist, suggesting that this is mediated by diminished degradation of SP (15).…”

Peptidergic sensory neurons in the control of vascular functions: Mechanisms and significance in the cutaneous and splanchnic vascular beds

“…1988). Further on, SP exerts a chemolactic action on monocytes (Ruff et al 1985) and granuiocytes (Helme et al 1987), and stimulates the adhesion of leucocytes to the vessel wall and their emigration into the inflamed tissue of the skin (Helme and Andrews 1985;Yano et al 1989;Umeno et al 1990). CGRP also causes granulocytes to infiltrate human skin (Piotrowski and Foreman 1986), whilst in rabbit skin CGRP is without effect on its own but potentiates granulocyte accumulation initiated by other stimuli (Buckley et al 1991).…”

Unilateral cervical vagotomy decreases the magnitude of neurogenic inflammation induced by capsaicin in the ipsilateral bronchial tree of rats

“…The trachea only receives sensory innervation from the paired vagus nerves Dalsgaard and Lundberg 1984;Saria et al 1985;Cadieux et al 1986). Capsaicin, when administered intravenously, can stimulate the sensory nerve endings to release tachykinins and provoke neurogenic inflammation in the airways of both right and left sides, phenomena such as increased vascular permeability in the tracheobronchial mucosa , bronchoconstriction (Saria et al 1985), neutrophil adherence to the tracheal mucosal venules (Umeno et al 1989(Umeno et al , 1990, degranulation of goblet cells (McDonald 1988b;Huang et al 1989;Kou et al 1990;Tokuyama et al 1990) and dilation of intercellular spaces in the surface epithelium of the tracheal mucosa (McDonald 1988b;Huang et al 1989).…”