PULMONARY SURFACTANT SYSTEM AND RADIATION PNEUMONITIS

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Pulmonary fibrosis and pneumonitis are inter-related and represent the spectrum of expression of lung injury to irradiation. Although a diffuse pneumonitis is a more dramatic and relatively early event following toxic doses of radiation, the fibrotic process is as lethal or debilitating albeit a later event. Both in the clinic and in the laboratory, a wide variety of dose/time fractionation schedules have been studied and have led to the proposition that the two processes of pneumonitis and fibrosis are due to different target cells, i.e. type II epithelial cells and the septal fibroblast respectively and are distinct in time as to the expression of the reaction. New evidence from our own investigations as well as others suggests this is a multicellular process with initiation and sustaining of the fibrogenic process through an intercommunication between different lung cells. That is, soon after irradiation there is the synthesis and secretion of numerous growth and inhibitory factors that occur for weeks to months during the so-called "latent" period after a lethal exposure. In fact, the genetic expression of injury probably occurs immediately, within hours and/or days, as there are genetic events which control and regulate the release of signals and receptors and control the dynamic sequence of events. A concise summary of target cells injured by irradiation is presented to clarify the pathophysiologic events and the hypothesized biological markers, i.e. biochemical and growth factors. The response to radiation injury is a complex process and needs to be investigated in terms of the new molecular physiology to explain the histopathologic events. The concept of a single target cell which can explain the dynamic sequence of events which occurs following lethal pulmonary irradiation is supplanted by that of multiple cell systems interacting. The so-called "latent" period of weeks or months to express radiation reactions is being replaced by appreciation of autocrine, paracrine and endocrine messages being sent immediately after the injurious exposure to irradiation by a variety of cells: epithelial, endothelial, fibroblasts and macrophages. The implementation of the process is by genetic reprogramming of the cell cycle, the response of a variety of growth factors and inhibiting factors, the alteration of specific cell receptors to receive these signals, and the resulting transduction and translation of these signals into post receptor cytoplasmic, nuclear and interstitial events.