NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea.
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.
Baluk
P
P
Department of Anatomy, University of California, San Francisco 94143-0130.
Bertrand
C
C
Geppetti
P
P
McDonald
D M
DM
Nadel
J A
JA
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002199:Capillary Permeability; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004396:Coloring Agents; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D007211:Indoles; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D009424:Nervous System Physiological Phenomena; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009942:Organometallic Compounds; D051381:Rats; D011916:Rats, Inbred F344; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D014132:Trachea / Q000098:blood supply; D014136:Tracheitis / Q000473:pathology / Q000503:physiopathology*
D001713:Biphenyl Compounds; D004396:Coloring Agents; D007211:Indoles; D009942:Organometallic Compounds; D018040:Receptors, Neurokinin-1; C015445:copper phthalocyanine; C066892:CP 96345