Early cellular events in pulmonary fibrosis.
In this review we have surveyed recent investigations of early cellular events in pulmonary fibrosis both in animal models and in human diseases. Analysis of the interactions of the numerous cell types in the lung following injury is an almost overwhelmingly complex enterprise. In the animal models experimental design has a profound effect on results, making it difficult to compare studies when species, fibrogenic agent, dose, route of exposure, schedule of administration, time course, and analytical methods may not be equivalent. In human diseases we are rarely able to obtain data at precisely the same time point in the course of the disease even among patients in the same study, and possible confounding variables present are legion. Transcending these difficulties for the moment, can we draw any conclusions from our current knowledge of early cellular interactions in pulmonary fibrosis? What is striking is not that there are so many agents that can potentially induce pulmonary fibrosis, but that the lung has such capabilities for recovery. Although the major effector cells may all initially participate in damaging the lung and initiating fibrosis, there is evidence that they may also have the capacity to participate in subsequent repair. Macrophages may initially recruit fibroblasts and stimulate them to proliferate, only to suppress them subsequently. Macrophage production of prostaglandins can lead to suppression of macrophage, neutrophil and lymphocyte responses, thus attenuating tissue injury and the development of fibrosis. Neutrophils may initially release toxic metabolites and enzymes that damage parenchyma. However, there is evidence that they may later play a role in attenuating fibrosis, perhaps through collagenase secretion, or through as yet unknown mechanisms. Lymphocytes may initially participate in a number of damaging ways by secreting chemoattractants for other cells and participating in destructive autoimmune processes. However, there is evidence that subpopulations of T cells may dramatically shift during the course of fibrosis, leading to attenuation of the process. It may thus be useful to consider irreversible pulmonary fibrosis as the end result of a process in which the balance of normal injury/repair mechanisms is disrupted. There is clearly no single "fibrogenic event." Rather, there seem to be a number of places where disruption of balance/repair processes may begin. In diseases of unknown etiology such as sarcoidosis or IPF, loss of control may occur at the genetic level, leading to the destructive alveolitis that is the apparent precursor of fibrosis.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D002455:Cell Division; D004804:Eosinophils / Q000473:pathology / Q000503:physiopathology; D004848:Epithelium / Q000473:pathology / Q000503:physiopathology; D005347:Fibroblasts / Q000473:pathology / Q000503:physiopathology; D008214:Lymphocytes / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology / Q000503:physiopathology; D008407:Mast Cells / Q000473:pathology / Q000503:physiopathology; D009504:Neutrophils / Q000473:pathology / Q000503:physiopathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D051381:Rats