Neutrophil-induced lung damage after hepatic ischemia and endotoxemia
| Autor: | Peitan Liu, G. M. Mcguire, Hartmut Jaeschke |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Pulmonary Circulation medicine.medical_specialty Time Factors Kupffer Cells Neutrophils Remote organ Lung injury Biochemistry Tirilazad mesylate chemistry.chemical_compound Ischemia Superoxides Physiology (medical) Internal medicine medicine Animals Lung Liver injury Analysis of Variance Superoxide business.industry Alanine Transaminase respiratory system medicine.disease Rats Inbred F344 Rats respiratory tract diseases Hepatic ischemia Endotoxins Endocrinology medicine.anatomical_structure Liver Salmonella enteritidis chemistry Reperfusion Immunology Tetradecanoylphorbol Acetate Trolox business Bronchoalveolar Lavage Fluid |
| Zdroj: | Free Radical Biology and Medicine. 20:189-197 |
| ISSN: | 0891-5849 |
| Popis: | Administration of Salmonella enteritidis endotoxin (0.5 mg ET/kg) during reperfusion (RP) after short-term hepatic ischemia (20 min) caused severe liver injury induced by Kupffer cells and neutrophils and a high mortality rate. To investigate potential lung damage in this model, lung wet-to-dry weight ratios (W/D) and broncho-alveolar lavage (BAL) protein content were determined after 4 h of reperfusion. Both parameters increased significantly during RP/ET (W/D: 4.4 +/- 0.1; BAL: 639 +/- 30 micrograms/ml) compared to controls (W/D: 3.5 +/- 0.1; BAL: 332 +/- 17). The antioxidants Trolox or tirilazad mesylate (U-74006F) effectively reduced the BAL protein increase. Alveolar macrophages were not activated; however, neutrophils isolated from the lung microvasculature of RP/ET animals showed a 300% increase of spontaneous and PMA-induced superoxide formation compared to controls (spontaneous: 1.4 +/- 0.5 nmol O2-/h/10(6) cells; PMA: 2.2 +/- 0.4). Complement factors and TNF-alpha injection induced a similar priming of vascular neutrophils for superoxide generation. Vascular neutrophil activation highly correlated with the severity of lung injury. It is concluded that neutrophils accumulated in the lung microvasculature were the major source of the oxidant stress and mainly responsible for lung injury under these conditions. Antioxidants such as tirilazad mesylate (U-74006F) may have therapeutic potential for attenuating lung injury induced by remote organ trauma and a systemic inflammatory response. |
| Databáze: | OpenAIRE |
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