Mechanisms of alveolar fibrosis after acute lung injury

In patients who have died following severe acute lung injury, a dramatic fibroproliferative response is found to have occurred within the alveolar air space, interstitium, and microvessels. The air space is obliterated by granulation tissue comprised of replicating mesenchymal cells, their connective tissue products, and an expanding network of intra-alveolar capillaries. In contrast, the vascular fibroproliferative response is dominated by mesenchymal cell replication and connective tissue deposition within the walls of microvessels. Although our current understanding of the signals regulating the fibroproliferative response following acute lung injury is limited, inferences can be made from in vivo studies of mesenchymal cell behavior and several better understood fibroproliferative processes, including wound healing and chronic fibrotic lung diseases. These inferences will serve as the starting point for a consideration of how growth factors, chemoattractants, and modulators of extracellular matrix deposition may interact to determine the time course and pattern of tissue response following acute lung injury. The goal in this discussion is to explore some of the biologic principles that will form the foundation for therapeutic interventions aimed at enhancing lung repair.