Decreased protein C activation is associated with abnormal collagen turnover in the intraalveolar space of patients with interstitial lung disease

Activation of the coagulation system in the alveolar space plays an importa nt role in the pathogenesis of interstitial lung disease (ILD) and pulmonar y fibrosis. The protein C (PC) pathway is the main modulator of coagulation activation. This study evaluated whether dysfunction of the PC pathway is associated with increased collagen synthesis in the intraalveolar space of patients with ILD. This study comprised 22 patients with ILD; of these, Eve had idiopathic pulmonary fibrosis (IPF), nine had sarcoidosis-associated n o, and eight had collagen vascular disease-associated ILD (CVD-ILD). Thromb in-antithrombin complex (TAT) was measured as a marker of coagulation activ ation. As markers of the PC pathway activity, the concentration of activate d PC-PC inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were measured and, as a marker of collagen synthesis, the concentration of aminoterminal propeptide of type III procollagen (PIIINP) was measured in bronchoalveolar lavage fluid (BALF) of ILD patients. TAT was significantly increased in BA LF from ILD patients as compared to control subjects. The concentrations of PIIINP were significantly elevated in patients with ILD as compared to hea lthy subjects. In contrast, the concentration of APC-PCI and the values of APC-PCI/PC ratio were significantly decreased in BALF from patients with IL D. BALF concentration of PIIINP was significantly and inversely correlated with the concentration of APC-PCI and with the APC-PCI/PC ratio. These Endi ngs suggest that dysfunction of the protein C pathway may have important ph ysiopathologic implications in the development of pulmonary fibrosis in ILD .