Upregulation of substance P receptors in angiogenesis associated with chronic airway inflammation in rats

Peter Baluk, Jeffrey J. Bowden, Peter M. Lefevre, Donald M. McDonald

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48 Citations (Scopus)

Abstract

-In rat airways, substance P released from sensory nerves induces plasma leakage via neurokinin-1 (NK1 ) receptors on endothelial cells. In pathogenfree rats, both leakage and endothelial NK1 receptors are most abundant in postcapillary venules. In Mycoplasma pulmonis-infected rats, extensive angiogenesis occurs in the tracheal mucosa. The capillary-sized (<10 μm in diameter) angiogenic blood vessels are abnormally sensitive to substance P. The aim of this study was to determine whether increased expression of NK1 receptors contributes to this abnormal sensitivity. Fischer 344 rats were infected with M. pulmonis and were challenged with substance P (5 μg/kg iv), and then plasma leakage in the tracheal mucosa was measured by extravasation of Monastral blue (30 nig/kg iv). NK1 receptors on endothelial cells were localized by immunohistochemistry. Five minutes after substance P, NK1 receptorimmunoreactive endosomes were five times more abundant in endothelial cells of angiogenic capillaries in M. pulmonisinfected rats than in corresponding capillaries in pathogenfree controls (17.1 ± 2.3 vs. 3.5 ± 0.4 endosomes/100 μm2 of endothelial surface). Endosomes were slightly more abundant in postcapillary venules 15-35 μm in diameter in infected rats (23.0 ± 0.6 vs. 19.2 ± 0.7 endosomes/100 μm2). Similarly, after substance P, angiogenic capillaries had much more Monastral blue labeling (area density: 18.8 ± 1.5 vs. 2.9 ± 0.5% of vessel wall), whereas postcapillary venules had about the same amount of labeling (36.0 ± 3.7 vs. 34.1 ± 1.8%). We conclude that increased expression of NK1 receptors, which are internalized into endosomes after ligand binding, contributes to the abnormal sensitivity of endothelial cells of angiogenic blood vessels to substance P in the airways of M. pulmonis-infected rats.

Original languageEnglish
Pages (from-to)L513-L523
JournalAMERICAN JOURNAL OF PHYSIOLOGY
Volume273
Issue number3 PART 1
Publication statusPublished - 1 Dec 1997

Keywords

  • Bronchusassociated lymphoid tissue
  • Endosomes
  • Mycoplasma pulmonis infection
  • Neurokinin-1 receptors
  • Plasma leakage
  • Tachykinins
  • Trachea
  • Vascular permeability

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