Mechanisms Of Pulmonary Injury Research Articles

Lung transcriptional profiling: insights into the mechanisms of ozone-induced pulmonary injury in Wistar Kyoto rats

Acute ozone-induced pulmonary injury and inflammation are well characterized in rats; however, mechanistic understanding of the pathways involved is limited. We hypothesized that acute exposure of healthy rats to ozone will cause transcriptional alterations, and comprehensive analysis of these changes will allow us to better understand the mechanism of pulmonary injury and inflammation. Male Wistar Kyoto rats (10–12 week) were exposed to air, or ozone (0.25, 0.5 or 1.0 ppm) for 4 h and pulmonary injury and inflammation were assessed at 0-h or 20-h (n = 8/group). Lung gene expression profiling was assessed at 0-h (air and 1.0 ppm ozone, n = 3–4/group). At 20-h bronchoalveolar lavage, fluid protein and neutrophils increased at 1 ppm ozone. Numerous genes involved in acute inflammatory response were up-regulated along with changes in genes involved in cell adhesion and migration, steroid metabolism, apoptosis, cell cycle control and cell growth. A number of NRF2 target genes were also induced after ozone exposure. Based on expression changes, Rela, SP1 and TP3-mediated signaling were identified to be mediating downstream changes. Remarkable changes in the processes of endocytosis provide the insight that ozone-induced lung injury and inflammation are likely initiated by changes in cell membrane components and receptors likely from oxidatively modified lung lining lipids and proteins. In conclusion, ozone-induced injury and inflammation are preceded by changes in gene targets for cell adhesion/migration, apoptosis, cell cycle control and growth regulated by Rela, SP1 and TP53, likely mediated by the process of endocytosis and altered steroid receptor signaling.

Progress in Understanding the Pathogenesis of Systemic Sclerosis with Lung Involvement: The Contribution of Proteomic Studies

Systemic sclerosis (SSc) is a chronic inflammatory disease involving the skin and various internal organs. SSc is characterized by microvascular dysfunction, activation of the immune system and tissue fibrosis. Endothelial cell damage seems to be the initiating factor, but the precise triggering events that underlie the development of the disease remain unclear. Lung involvement is a frequent complication, which causes increased morbidity and mortality in patients with SSc. In particular, pulmonary arterial hypertension and interstitial lung disease are the two major clinical diseases that affect SSc patients, but the current treatments appear to have no satisfying effects on these pulmonary complications, until yet. Recently researches using innovative technologies have highlighted several peptides that might contribute to better understand the underlying pathogenic mechanisms of pulmonary injury and could promote more effective therapeutic strategies for SSc patients. Here, we focus on the major proteomic studies on biological fluid from patients with SSc.

Pulmonary responses to oil fly ash particles in the rat differ by virtue of their specific soluble metals.

Occupational exposure to residual oil fly ash (ROFA) particulate has been associated with adverse respiratory health effects in humans. We hypothesized that ROFA collected at different sites within an oil burning power plant, by virtue of its differing metal and sulfate composition, will induce differential lung injury. Ten ROFA samples collected at various sites within a power plant were analyzed for water- and 1.0 M HCl-leachable arsenic (As), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), zinc (Zn), and sulfur by inductively coupled plasma-atomic emission spectroscopy. All ROFA samples contained variable amounts of leachable (water-extractable) and 1.0 M HCl-extractable Fe, V, and/or Ni. All other metals, except Zn (ROFA No. 1 contained 3.43 and No. 3, 6.35 micrograms/mg Zn), were present in negligible quantities (< 1.0 microgram/mg) in the water extract. In vivo pulmonary injury from exposure to whole saline suspensions of these ROFA was evaluated. Male, SD rats (60 days old) were intratracheally instilled with either saline or saline suspension of whole ROFA (< 3.0 mass median aerodynamic diameter) at three concentrations (0.833, 3.33, or 8.33 mg/kg). After 24 h, lungs were lavaged and bronchoalveolar lavage fluid (BALF) was analyzed for cellular influx and protein content as well as lactate dehydrogenase (LDH) and N-acetyl glucosaminidase (NAG) activity and total hemoglobin as indicators of lung injury. ROFA-induced increases in BALF protein and LDH, but not neutrophilic inflammation, were associated with its water-leachable total metal, Ni, Fe, and sulfate content. However, the neutrophilic response following ROFA exposure was positively correlated with its water-leachable V content. Modest lung injury was observed with the ROFA samples which contained the smallest amounts of water-leachable metals. The ability of ROFA to induce oxidative burst in alveolar macrophage (AM) was determined in vitro using a chemiluminescence (CL) assay. AM CL signals in vitro were greatest with ROFA containing primarily soluble V and were less with ROFA containing Ni plus V. In summary, ROFA-induced in vivo acute pulmonary inflammation appears to be associated with its water-leachable V content; however, protein leakage appears to be associated with its water-leachable Ni content. ROFA-induced in vitro activation of AM was highest with ROFA containing leachable V but not with Ni plus V, suggesting that the potency and the mechanism of pulmonary injury will differ between emissions containing V and Ni.

Pulmonary Responses to Oil Fly Ash Particles in the Rat Differ by Virtue of Their Specific Soluble Metals

Occupational exposure to residual oil fly ash (ROFA) particulate has been associated with adverse respiratory health effects in humans. We hypothesized that ROFA collected at different sites within an oil burning power plant, by virtue of its differing metal and sulfate composition, will induce differential lung injury. Ten ROFA samples collected at various sites within a power plant were analyzed for water- and 1.0 M HCl-leachable arsenic (As), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Si), lead (Pb), vanadium (V), zinc (Zn), and sulfur by inductively coupled plasma-atomic emission spectroscopy. All ROFA samples contained variable amounts of teachable (water-extractable) and 1.0 M HCl-extractable Fe, V, and/or Ni. All other metals, except Zn (ROFA No. 1 contained 3.43 and No. 3, 6.35 μg/mg Zn), were present in negligible quantities (<1.0 μg/mg) in the water extract In vivo pulmonary injury from exposure to whole saline suspensions of these ROFA was evaluated. Male, SD rats (60 days old) were intratracheally instilled with either saline or saline suspension of whole ROFA (<3.0 mass median aerodynamic diameter) at three concentrations (0.833, 3.33, or 8.33 mg/kg). After 24 h, lungs were lavaged and bronchoalveolar lavage fluid (BALF) was analyzed for cellular influx and protein content as well as lactate dehydro-genase (LDH) and N-acetyl glucosaminidase (NAG) activity and total hemoglobin as indicators of lung injury. ROFA-induced increases in BALF protein and LDH, but not neutrophilic inflammation, were associated with its water-leachable total metal, Ni, Fe, and sulfate content. However, the neutrophilic response following ROFA exposure was positively correlated with its water-leachable V content Modest lung injury was observed with the ROFA samples which contained the smallest amounts of water-leachable metals. The ability of ROFA to induce oxidative burst in alveolar macrophage (AM) was determined in vitro using a chemiluminescence (CL) assay. AM CL signals in vitro were greatest with ROFA containing primarily soluble V and were less with ROFA containing Ni plus V. In summary, ROFA-induced in vivo acute pulmonary inflammation appears to be associated with its water-leachable V content; however, protein leakage appears to be associated with its water-leachable Ni content. ROFA-induced in vitro activation of AM was highest with ROFA containing leachable V but not with Ni plus V, suggesting that the potency and the mechanism of pulmonary injury will differ between emissions containing V and Ni.

Mechanisms of pulmonary injury

Considered here are recent concepts concerning pathogenetic mechanisms underlying alterations in lung tissue structure and function. Mechanisms of pulmonary injury are described and include (1) the capacity of proteolytic enzymes to induce experimental pulmonary emphysema with particular emphasis on the effects of elastases and collagenases on connective tissue components, (2) the effects on distal lung units of specific chemical toxins, and (3) the capacity of the circulating polymorphonuclear leukocyte to induce pulmonary injury by the action of lysosomal enzymes. Evidence is reviewed which indicates a predominant role for alterations in alveolar elastin as the basis for alveolar tissue destruction along with the delayed effects on lung function and morphology of proteolytic injury. Newer developments in the understanding of the functions of the alpha 1-globulin and other proteolytic enzyme inhibitors in the respiratory tract are considered. The special characteristics of cell damage induced by noxious agents such as cadmium, nitrogen dioxide, ozone, high oxygen concentrations as well as alpha-napthyl-thiourea, alloxan and paraquat are discussed. Finally, the proteolytic capacity of the polymorphonuclear leukocyte and the links between the leukocyte proteases and the activation of leukokinin and bradykinin generating systems are summarized, and their role in the tissue injury induced by antibody-antigen reactions, shock lung and nonspecific tissue damage is indicated.

Mechanisms of pulmonary injury : Turino GM, Rodriguez JR, Greenbaum LM, Mandl I: Am J Med 57: 000-000, 1974

Mechanisms of pulmonary injury : Turino GM, Rodriguez JR, Greenbaum LM, Mandl I: Am J Med 57: 000-000, 1974

Mechanism of pulmonary injury after oxygen therapy

Summary o 1.From the experimental studies it is concluded that pulmonary O 2 tolerance is increased by intermittent exposure. 2.High O 2 tensions promote atelectasis, but this can effectively be managed by regular and frequent hyperinflation. 3.The extent of chronic PT is closely correlated with the O 2 tension of the blood perfusing the lung when PO 2 of the inspired gas is kept constant. 4.The threshold and tolerance to O 2 therapy is reviewed and recommendations for therapy are made.