Acute lung injury. Pathogenesis of intraalveolar fibrosis

Abstract

In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth-promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth-promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38-kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication.