Decreased distribution of lung epithelial junction proteins after intratracheal antigen or lipopolysaccharide challenge: correlation with neutrophil influx and levels of BALF sE-cadherin.
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.
D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000378:metabolism*; D008168:Lung / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000378:metabolism*; D062793:Occludin; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D013997:Time Factors; D014132:Trachea / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
D015820:Cadherins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein