Decreased distribution of lung epithelial junction proteins after intratracheal antigen or lipopolysaccharide challenge: correlation with neutrophil influx and levels of BALF sE-cadherin

Am J Respir Cell Mol Biol. 2002 Oct;27(4):446-54. doi: 10.1165/rcmb.4776.

Abstract

Distribution of airway junctional complex proteins after antigen or lipopolysaccharide challenge in sensitized or naive mice, respectively, was investigated. E-cadherin immunoreactivity was detected continuously along neighboring epithelial cell borders and between adjacent alveolar epithelial cells in naive and saline-challenged mice. Occludin and ZO-1 immunoreactivity were observed in the tight junction areas. Both challenges induced changes in epithelial morphology and phenotype, accompanied initially by focal loss of epithelial E-cadherin that increased in size with time and number of allergen challenges. Allergen challenge also led to focal loss of occludin and ZO-1. Western blot analysis revealed increased levels of sE-cadherin in lavage fluid after either challenge, and this increase correlated with lavage neutrophil numbers (P = 0.002). Immunocytochemistry of lavage cells 6 h after either challenge revealed E-cadherin epitopes within cytoplasmic vacuoles of neutrophils, the major cell type. In contrast, peripheral blood neutrophils or tissue neutrophils before epithelial transmigration were negative, suggesting that in airway inflammation, E-cadherin extracellular domain is cleaved by neutrophils during epithelial penetration, instigating the destabilization of adherens and tight junctions. This junctional deterioration could lead to a progressive decrease in epithelial integrity and induce alterations in epithelial morphology, with consequent enhanced paracellular transit of antigens and pathogens.

MeSH terms

  • Adherens Junctions / metabolism*
  • Animals
  • Blotting, Western
  • Bronchoalveolar Lavage Fluid*
  • Cadherins / metabolism*
  • Cell Movement
  • Escherichia coli / metabolism
  • Humans
  • Immunohistochemistry
  • Lipopolysaccharides / metabolism*
  • Lung / pathology*
  • Male
  • Membrane Proteins / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Fluorescence
  • Neutrophils / metabolism*
  • Occludin
  • Phenotype
  • Phosphoproteins / biosynthesis*
  • Pulmonary Alveoli / metabolism
  • Tight Junctions / metabolism*
  • Time Factors
  • Trachea / metabolism*
  • Zonula Occludens-1 Protein

Substances

  • Cadherins
  • Lipopolysaccharides
  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Ocln protein, mouse
  • Phosphoproteins
  • TJP1 protein, human
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein