Cell and Animal Models of Lung Injury

This chapter describes cell and animal models used in studying the mechan-

isms, pathophysiology, and therapy of lung injury. The complex phenomen-

ology of lung injury requires complementary investigations in whole animals in vivo, lung tissue in situ, and cells in vitro. A variety of specific

models and assessments within these general categories are used in research

applications. In vitro research on lung injury examines cultured cell lines as

well as isolated native pulmonary or leukocytic cells in suspension or cul-

ture. In vitro research also includes studies on cultured lung tissue explants

exposed to injury stimuli. The responses of specific cells in lung tissue are

also often examined in situ during acute and chronic injury. Cell-based

research is particularly important in mechanistic assessments of injury-related signal transduction pathways, transcriptional events, and

other biochemical and regulatory processes. Such research is complemen-

ted by animal studies in vivo that elucidate responses to injury at the level

of the whole organism. Multiple animal models of acute and chronic lung

injury are summarized in this chapter. Examples are also presented to illus-

trate specific experimental assessments relating to antioxidant activity,

DNA damage, cell proliferation and death, and pulmonary surfactant

alterations in hyperoxia=oxidant-induced injury. Further coverage of experimental models used in lung injury research is given in Chapter 11 (geneti-

cally modified mouse models of lung injury and repair) and Chapter 12

(models and considerations relevant for inhalation toxicology).