Laminin γ2 fragments are increased in the circulation of patients with early phase acute lung injury

OBJECTIVE: Laminin-5, a cell adhesive molecule expressed solely by epithelium, is known to enhance epithelial cell migration and repair of injured epithelium, after its essential component γ2-chain is processed proteolytically. Our previous study revealed circulating levels of amino-terminal fragment of laminin γ2-chain (G2F) reflect epithelial tumor invasiveness in carcinoma patients, but its physiological role in alveolar epithelial injury remains unknown. DESIGN: Sampling of epithelial lining fluids or pulmonary edema fluids from patients with acute lung injury (ALI) or related diseases was performed. Plasma samples were obtained from them at the time of disease onset or later. G2F concentrations were determined by immunoassay constructed by ourselves. RESULTS: We found a significantly higher amount of G2F in pulmonary edema and epithelial lining fluids of patients with ALI, as compared with those with the other respiratory diseases. Their plasma levels were also elevated significantly early at the onset of ALI (mean ± SD; 147 ± 82 ng/ml in non-surviving and 90 ± 56 in surviving patients) as compared with those in the patients with cardiogenic pulmonary edema (59 ± 36) or idiopathic pulmonary fibrosis (37 ± 17), indicating alveolar epithelium rapidly secrete laminin-5 in ALI. At 5 days after onset, non-surviving patients maintained higher plasma concentrations (152 ± 84), but in contrast, the levels in surviving patients declined (71 ± 35), suggesting secretion of laminin-5 was suppressed, associated with recovery from ALI. CONCLUSION: Circulating G2F may be a biomarker for alveolar laminin-5 secreted early at disease onset in ALI, potentially regulating alveolar re-epithelialization.