Lung injury: cell-specific bioactivation/deactivation of circulating pneumotoxins

Abstract

Many of the blood-borne xenobiotics which result in injury to the lung are not inherently pneumotoxic but cause damage within the target cells following metabolic activation. This injury is usually restricted to those cells capable of bioactivation and thus, in addition to its clinical significance, it provides a valuable indicator of the normal metabolic activity within the numerous cell types present in lung. Not surprisingly, injury does not simply reflect the presence or absence of a particular enzyme but rather the balance between mechanisms for activation and deactivation. A change in the balance between different enzymes may also determine whether activation results in injury or tumorigenesis (Foster et al. 1992). Changes in particular types of cells cannot be determined by analysing whole lung homogenates. Isolation of particular cell types can provide valuable information but this approach does not address the differences between adjacent cells of the same type (Forkert & Moussa 1989; Dinsdale et al. 1992). Further progress may require the correlation of the injury with the status of individual cells; the quantitation of histochemical and immunocytochemical data is notoriously labour intensive but this approach may well be inescapable.