Molecular Mechanisms in Acute Lung Injury

Abstract

This chapter explores the experience in the use of lung inflammatory models, which have provided information on the role of various inflammatory mediators and their sequence of engagement. This information has provided insights into potential interventional approaches for the suppression of inflammatory processes in humans. The use of animal models of lung inflammation has allowed for the probing of pathways of inflammation responsible for injury. Although the models do not necessarily extrapolate to lung inflammatory diseases in humans, they have permitted a detailed dissection of events that ultimately lead to damage of interstitial capillary endothelial cells and alveolar epithelial cells. In this chapter, models of inflammatory injury in rat lung are discussed: injury occurring after systemic activation of complement and injury developing after alveolar deposition of either IgG or IgA immune complexes. In each model, there are similarities but also distinctive differences that have provided insights into diverse pathways by which the inflammatory response causes tissue injury. This chapter also demonstrates how the in vitro use of endothelial cell monolayers has provided an approach to understanding the mechanisms by which activated neutrophils injure endothelial cells