Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis is a chronic inflammatory fibrotic disorder localized to the lower respiratory tract and characterized by an alveolitis dominated by alveolar macrophages and neutrophils, and to a lesser extend, lymphocyte and eosinophils.

The disease usually presents as dyspnea on exertion, the chest x-ray shows diffuse reticulonodular infiltrates, and analysis of lung function reveals restrictive abnormalities. Evaluation of the inflammatory cells recovered by Bronchoalveolar lavage has lead to the concept that the cell responsible for directing the process of scar formation is the alveolar macrophage, a cell that normally defends the alveolar structures by phagocytosing infectious agents and particulates. In Idiopathic Pulmonary Fibrosis, for reasons not completely understood but likely related to immune complexes formed in the milieu, the alveolar macrophages express several genes that code for potent polypeptide mediators capable of recruiting fibroblasts and signaling them to proliferate. The consequence is that fibroblasts are abundant in the milieu of chronic damage. Since fibroblast secrete a collagenous extracellular matrix, more collagen i.e., a scar, forms.

Among the polypeptide mediators released by alveolar macrophages of Idiopathic Pulmonary Fibrosis patients is fibronectin, a 220-kDA dimeric glycoprotein that interacts with the connective tissue matrix and with specific receptors on fibroblasts. Studies of fibronectin gene expression in alveolar macrophages demonstrate that fibronectin mRNA levels correlate with fibronectin release. Indeed, alveolar macrophages recovered from Idiopathic Pulmonary Fibrosis patients contain more fibronectin mRNA than alveolar macrophages of normals.
Idiopathic Pulmonary Fibrosis