Oxygen Radical Production by Alveolar Inflammatory Cells in Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease characterized by the accumulation of alveolar macrophages (AMs) and neutrophils in the lower respiratory tract, parenchymal cell injury, and fibrosis of the alveolar structure. Reactive oxygen intermediates (ROI) are claimed to be a major cause of tissue damage in IPF; however, the source of ROI has not been unequivocally identified. AMs, as well as neutrophils, are capable of releasing these agents. The contributions of these possible sources are not known. To address this question, we evaluated the spontaneous and stimulated (PMA or zymosan) ROI release of total bronchoalveolar cells and isolated AMs in 14 patients with IPF by means of luminol-enhanced chemiluminescence. Bronchoalveolar lavage (BAL) cells from 17 individuals without any signs of inflammation served as controls. In comparison with the controls, the spontaneous as well as the stimulated ROI release of total BAL cells in IPF are markedly increased (20,763.9 +/- 5,079.3 versus 2,509.5 +/- 300.6 counts/10 s/2.10(5) cells, spontaneously, IPF versus control; 106,819.3 +/- 33,802.8 versus 8,919 +/- 1,357.9 PMA induced; 41,597.1 +/- 8,442.6 versus 6,223.8 +/- 1,025.1 zymosan induced, p less than 0.001). Measurement of the ROI release of purified AMs revealed that these cells produce the bulk part of ROI released by BAL cells (84%). In spite of the fact that, on a per cell basis, the ROI release of neutrophils is 1.7-fold of that of AMs, there is no correlation between the ROI production of total BAL cells and the percentage of neutrophils in BAL, demonstrating a minor role of these cells in the generation of the total ROI burden in IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxidized BAL fluid proteins in patients with interstitial lung diseases

“…Taken together, all three measures are complementary and may be useful in describing the oxidant status of the lung. Our finding that oxidatively modified proteins (nmol carbonyl·mL -1 BALF) are significantly accumulated in the IPF-NS and SARC-NS groups, is consistent with the reported evidence for an activation of the respiratory burst of AMs in these groups [10,12]. In contrast to these results, we found no changes in this parameter in the IPF-S and ASB-EXS groups.…”

“…Oxidizing air pollutants, such as ozone or cigarette smoke, might damage bronchoalveolar lavage fluid (BALF) proteins directly by oxidation [3,[7][8][9], or by triggering an inflammatory response. In patients with idiopathic pulmonary fibrosis (IPF), AMs and PMNs dominate the inflammatory cell population in the lower respiratory tract, releasing ex-vivo more oxidants both spontaneously and after stimulation than do cells from healthy nonsmoking individuals [10]. Similar results are obtained with BALF cells from smokers [11] or patients with sarcoidosis (SARC) [12].…”

Protective Effect of Ambroxol against Paraquat-induced Pulmonary Fibrosis in Rats

“…Oxygen free radicals can react with unsaturated fatty acids to cause peroxidation of essential membrane lipids in the plasmalemma or intracellular organelles (5,16,17). Lipid peroxidation is generally monitored by measuring MDA which results from free radical damage to membrane components of the cells and it is one of the production of reactive oxygen species.…”

Effect of Lecithinized-Superoxide Dismutase on the Interstitial Pneumonia Model Induced by Bleomycin in Mice.

“…Recently, oxygen radicals such as superoxide anion (02-) have been suggested to be related to the occurrence and exacerbation of interstitial pneumonia (1). Super oxide dismutase (SOD) is normally present in cells at a sufficient level to scavenge intracellular 02-.…”