ABSTRACT
The fibroproliferative phase of acute lung injury (ALI) is characterized by impaired gas exchange and severely reduced lung compliance as a result of progressive accumulation of interstitial and alveolar cells and matrix. The critical feature of this late stage of the injury-repair continuum is the disruption of normal alveolar architecture. This disruption leads to dysfunction in the liquid and protein barrier functions of the lung and in the diffusion properties of the alveolar-capillary structures. The restoration of normal lung architecture and function requires temporal and spatial coordination of alveolar proteolysis, cell migration and proliferation, angiogenesis, matrix synthesis, epithelial cell repopulation, and apoptosis (1-6). These responses are dependent on complex and dynamic interactions between growth factors/cytokines/chemokines, cells of diverse lineage, and their surrounding provisional matrix. It has been assumed that the intact alveolar basement membrane provides a critical roadmap for the remodeling and restoration of normal lung architecture after injury. Unfortunately, following a myriad of intravascular or inhaled insults, a series of temporally and spatially overlapping injury and repair events all too often results in a dysfunctional, fibrotic lung. This chapter will discuss the clinical, biochemical, and cell-matrix interactive events that lead to fibroproliferative repair after lung injury.
