AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 263-L269, Copyright © 1995 by American Physiological Society
NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea
P. Baluk, C. Bertrand, P. Geppetti, D. M. McDonald and J. A. Nadel
Department of Anatomy, University of California, San Francisco 94143-0130.
In neurogenic inflammation, tachykinins trigger the adhesion of neutrophils
and eosinophils to leaky venules. The goals of the present study were to
determine whether this leukocyte adhesion is mediated by neurokinin type 1
(NK1) receptors and to determine whether the amount of leukocyte adhesion
corresponds to the amount of plasma leakage. Anesthetized rats were
injected intravenously with substance P, the NK1 receptor agonist [Sar9,
Met(O2)11]-substance P, or the NK2 receptor agonist [beta-Ala8]neurokinin
A-(4-10). Five minutes later, the adherent neutrophils and eosinophils in
blood vessels of the tracheal mucosa were stained histochemically and
plasma leakage was quantified, as assessed by the extravasation of
Monastral blue. Substance P and the NK1 agonist caused similar amounts of
leukocyte adhesion, but the NK2 agonist had no effect. Pretreatment with
the NK1 receptor antagonist CP-96,345 (4 mg/kg iv), before challenge with
substance P, capsaicin, or aerosol hypertonic saline, reduced the amount of
neutrophil adhesion by 56%, 93%, and 57% and reduced the amount of
eosinophil adhesion by 70%, 83%, and 65%, respectively. Plasma
extravasation was decreased by 89%, 95%, and 94%. The number of adherent
neutrophils in the trachea was strongly correlated with the number of
adherent eosinophils (r2 = 0.61). The greatest amount of leukocyte adhesion
occurred in larger diameter venules than did the maximal amount of
Monastral blue leakage. We conclude that NK1 receptors mediate the adhesion
of neutrophils and eosinophils as well as the plasma leakage triggered by
substance P, capsaicin, or hypertonic saline. This leukocyte adhesion
evidently does not occur at exactly the same sites as the plasma leakage.
