Pathogenesis of fibrosis in acute lung injury.
The anatomic changes that occur in response to acute lung injury significantly impair gas exchange. As is the case with skin wounds, a fibroproliferative response follows lung injury. In the lungs, however, this can result in life-threatening obliteration of alveolar air spaces. A better understanding of the mechanisms involved in lung repair may allow the development of therapies that regulate the fibroproliferative response. Studies from our laboratory have identified a peptide in bronchoalveolar lavage fluid from patients with acute lung injury that promotes the migration and replication of lung fibroblasts. This peptide is related to platelet-derived growth factor (PDGF) antigenically as well as by receptor-binding criteria; its molecular weight is 14 kilodaltons (kDa) as compared to 29 kDa for PDGF. Despite the potent activity of the 14 kDa peptide, however, such a growth signal may not be absolutely required for tissue granulation. The possibility that lung fibroblasts from patients with acute lung injury might be capable of dividing without exogenous stimulation will be examined. Another theoretical consideration is the signals that regulate termination of the fibroproliferative response. Insights into the molecular mechanisms involved in lung repair may result in therapies that modulate the sometimes maladaptive fibroproliferative response following acute lung injury.
Bitterman
P B
PB
Department of Pulmonary and Critical Care Medicine, University of Minnesota Medical Center, Minneapolis 55455.
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002454:Cell Differentiation; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D005355:Fibrosis; D006133:Growth Substances / Q000737:chemistry / Q000502:physiology; D006801:Humans; D008970:Molecular Weight; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor