Determinants of lung response to breakdown in epithelial barrier function. (a) Coordinated processes of tissue factor/factor VII complexes initiating thrombin formation and plasminogen activation by urokinase (uPA). Plasmin facilitates initial exudate turnover. Ingrowth of fibroblasts and organization of exudates into a collagenous matrix occurs quickly. (b) Maintenance of epithelial integrity, resorption of ECMs by AMs, and fibroblast apoptosis favor resolution. (c) Epithelial cell apoptosis, activation of receptors of the profibrotic cytokines thrombin, leukotrienes, and TGF-β₁, and persistence of the ECM secondary to excess protease inhibitors (PAI-1 and tissue inhibitor of metalloprotease) with accumulation of fibroblast growth factors (IGF, PDGF, CTGF) favors fibrosis.