title: Claudin-4 levels are associated with intact alveolar fluid clearance in human lungs.
abstract: The removal of edema from the air spaces is a critical function of the alveolar barrier requiring intact tight junctions. Alveolar fluid clearance contributes to graft function after transplantation and is associated with survival in patients with acute lung injury. Claudin-4 concentrations are known to increase during lung injury and the loss of claudin-4 decreases alveolar fluid clearance in mice. This study was therefore undertaken to evaluate whether differences in lung expression of the tight junction protein claudin-4 are associated with alveolar fluid clearance or clinical measures of lung function. Alveolar fluid clearance rates were measured in ex vivo perfused human lungs not used for transplantation and were compared with histological lung injury and clinical measures of lung injury in the donors. Claudin-4 staining demonstrated a positive correlation with alveolar fluid clearance (Spearman rank correlation [r(s)] = 0.71; P < 0.003); however, claudin-4 staining was not strongly associated with histological measures of lung injury. The expression of other tight junction proteins (including ZO-1) was not associated with alveolar fluid clearance or claudin-4 levels. Claudin-4 staining was lower in lungs from donors with greater impairment in respiratory physiology. These data suggest that claudin-4 may promote alveolar fluid clearance and demonstrate that the amount of claudin-4 expressed may provide specific information regarding alveolar epithelial barrier function that strengthens the link between histological changes and physiological impairment.
authors: San Francisco VA Medical Center, University of California San Francisco, San Francisco, California, USA.
authors: Deepti
authors: D
authors: Rokkam
authors: Michael J
authors: MJ
authors: Lafemina
authors: Jae Woo
authors: JW
authors: Lee
authors: Michael A
authors: MA
authors: Matthay
authors: James A
authors: JA
authors: Frank
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001826:Body Fluids / Q000737:chemistry*; D062506:Claudin-4; D057167:Claudins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011654:Pulmonary Edema / Q000378:metabolism*; D019108:Tight Junctions
chemical_list: D015415:Biomarkers; C568157:CLDN4 protein, human; D062506:Claudin-4; D057167:Claudins; C568158:Cldn4 protein, mouse