Alteration of tight junctions in pulmonary microvascular endothelial cells in bleomycin-treated rats.
Macrophages and eosinophils that infiltrate the lung interstitium are active promoters of bleomycin (BLM)-induced pulmonary fibrosis. Leukocyte infiltration indicates disrupted barrier function in endothelial cells. The aims of this study were to investigate tight junctions (TJs) and their regulation of zonula occludens-1 (ZO-1) proteins in pulmonary microvascular endothelial cells (PMVECs) during BLM-induced pulmonary fibrosis and to compare the BLM model with the pneumococcus-induced pneumonia model of lung injury. The results revealed that the majority of PMVEC TJs were in an open state in BLM-treated tissue, where PMVEC paracellular permeability remained consistently higher than in controls. Macrophage accumulation in the lung interstitium was also significantly higher than in controls. Alteration of ZO-1 protein expression further supported the apparent disruption in PMVEC TJs in tissues from BLM-treated rats. These changes were markedly different from the concurrent changes in pneumococcus-infected rats. The findings suggest that changes in the ZO-1 proteins of PMVECs underlie the sustained disruption of TJs in BLM-treated animal models of pulmonary fibrosis. This dysfunction of paracellular barriers directly leads to the sustained infiltration of leukocytes and corresponding cytokine secretion, proliferation of fibroblasts, and progression of pulmonary fibrosis.
Yin
Qian
Q
Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xinsi Road, Xi'an 710038, PR China.
Nan
Haiyan
H
Yan
Linfeng
L
Huang
Xiaofeng
X
Wang
Wei
W
Cui
Guangbin
G
Wei
Jingguo
J
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects; D002452:Cell Count; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D018613:Microscopy, Confocal; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000096:biosynthesis; D011018:Pneumonia, Pneumococcal / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D062826:Zonula Occludens-1 Protein
D008565:Membrane Proteins; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D001761:Bleomycin