chapter  7
42 Pages

Roles of Reactive Oxygen and Nitrogen Species in Lung Injury

WithIan C. Davis, John D. Lang, Sadis Matalon

This chapter covers reactive oxygen and nitrogen species and their importance in inflammatory lung injury. As described in prior chapters, the

pathophysiology of lung injury is multifaceted, and includes the elaboration

of reactive oxygen and nitrogen species by inflammatory cells. Reactive

oxygen and nitrogen species are of considerable importance in innate

immunity and cellular regulation, but their release also results in collateral

damage to lung tissue that can ultimately compromise both gas exchange

and host defense. For example, reactive nitrogen species (RNS) produced

by macrophages in the presence of physiologic CO2 tensions can induce nitration of surfactant protein A (SP-A) and compromise its ability to act

as a collectin during host defense. Endogenous reactive oxygen and nitro-

gen species can also cause cell and tissue injury by a variety of other

mechanisms. In addition, exogenous reactive oxygen and nitrogen species

can also be involved in generating lung injury (e.g., from environmental

exposure to hyperoxia, ozone, nitric oxide, or related gases). This chapter

reviews the fundamental chemistry of reactive oxygen and nitrogen species,

as well as their positive and negative biological effects. Emphasis is on the roles of reactive species in acute injury and pulmonary disease based on basic

science and clinical perspectives. Pulmonary antioxidant defenses against

reactive oxygen and nitrogen species are also discussed. Therapeutic applica-

tions targeting oxidant-related pathophysiology are noted, with further

details on antioxidant therapies for lung injury given later in Chapter 16.