Oligo-2,5-Adenylate Synthetase in Pulmonary Sarcoidosis and Idiopathic Pulmonary Fibrosis

Oligo-2,5-Adenylate Synthetase in Pulmonary Sarcoidosis and Idiopathic Pulmonary FibrosisTreatment of cells with all types of interferon (IFN) the induction of oligo-2′,5′-adenylate synthetase (2,5AS) which is responsible for the synthesis of 2′-5′-linked oligomers of adenosine (2,5a). The enzyme product 2,5A itself has the ability to inhibit protein synthesis and to regulate cell growth. In this regard, 2,5AS plays a very important role in the mechanism of the action of IFN. This enzyme activity thus reflects the degree of IFN exposure to cells in vivo. A simple and rapid biochemical assay was developed by Shatter et al for detecting the activity of 2,5AS. By measuring the 2,5AS activity, we can estimate IFN production in the environment of the cells analyzed.
Recent studies demonstrated that IFN is an important mediator of granulomatous lung disorders and pulmonary fibrosis. Interferon, especially IFN-gamma, is known to be a potent activator of macrophages and one of the defined cytokines to most relevance to the generation of granulomas. By IFN-gamma, mRNA of platelet-derived growth factor was reported to be up-regulated in pulmonary alveolar macrophages (PAM) of idiopathic pulmonary fibrosis (IPF) and sarcoidosis (SAR). It is thought that IFN may be related to the pathogenesis of these diffuse lung disorders. In order to estimate IFN production both in the circulation and the alveolar space of patients with SAR and IPF, we measured the levels of 2,5AS activity in peripheral blood mononuclear leukocytes (PBML) and bronchoalveolar lavage fluid (BALF) cells. buy allegra

Patients and Healthy Controls
SAR: Fourteen untreated patients had a compatible clinical picture of SAR (compatible chest radiographic findings, including enlargement of bilateral pulmonary hilar and/or paratracheal lymph nodes with lung parenchymal infiltrates, and biopsy evidence of noncaseating epithelioid cell granuloma) without any evidence of mycobacterial, fungal, or parasitic infection. None had a history of exposure to organic or inorganic materials known to cause granulomatous lung disorders. Five male and nine female patients ranged in age from 20 to 79 years. Five patients were smokers and nine were nonsmokers.
IPF: Nine patients were diagnosed as having IPF according to clinical symptoms, chest radiographic findings, and physiologic studies, including the analysis of lung biopsy specimens. Six male and three female patients ranged in age from 53 to 73 years. These patients had not received steroid therapy. Seven patients were smokers and two were nonsmokers.
Normal Controls (NC): Eight healthy volunteers (six male and two female) ranged in age from 24 to 32 years and they had no evidence of lung disorders shown by physical examination, chest radiograph, and pulmonary function test findings. Four volunteers were smokers and four were nonsmokers.
Collection ofPBML
Peripheral blood of patients and healthy donors was obtained by venipuncture. The PBML were obtained from heparinized blood by Ficoll-Hypaque cushion (Pharmacia, Piscataway, NJ).

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