Expression of integrin alpha v beta 6 in rats with ventilator-induced lung injury and the attenuating effect of synthesized peptide S247
Qingping Wu, Ping Gui, Shanglong Yao, Huiyun Xiang
Med Sci Monit 2008; 14(2): BR41-48
High tidal volume ventilation can cause inflammatory reaction in lungs. Integrins are associated with regulating lung inflammation and edema following acute lung injury. Integrin alpha v beta 6 expression in ventilator-induced lung injury (VILI) and the ability of the RGD-peptidomimetic agent S247 to attenuate VILI in rats were investigated.
Material and Method: Eighteen adult male rats were assigned to three groups: controls (C: n=6) with no ventilation; high tidal volume lung ventilation (H: n=6); and such ventilation after treatment with S247 (HS: n=6). HS was injected with 50 mg/kg S247 18 h before and then i.p injection every 3 h until the start of ventilation. The others received saline. Assessed were lung histopathology, wet-to-dry weight ratios, total protein content, white blood cell (WBC) counts, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha) concentrations in the bronchoalveolar lavage fluid (BALF) and integrin alpha v beta 6 mRNA and protein expression.
Results: Wet-to-dry weight ratios and BALF WBCs and total protein content were different among the groups (p<0.01). Lung injury score and integrin alpha v beta 6 mRNA level were lower in HS than in H (p<0.01). Integrin alpha v beta 6-positive staining was mainly on alveolar walls and the immunoreactivity of HS was clearly less than in H. TNF-alpha was not detected in C and was significantly lower in HS than in H (p<0.05). MIP-2 concentration in H was higher than in C and HS (p<0.01).
Conclusions: Pretreatment with S247 attenuated VILI, suggesting pulmonary epithelial integrins are involved in its pathogenesis and agents such as S247 may be useful in treating it.
Keywords: Rats, Sprague-Dawley, Respiration, Artificial - adverse effects, RNA, Messenger - metabolism, Rats, Organic Chemicals - pharmacology, Oligopeptides - agonists, Lung Injury, Leukocyte Count, Lung - metabolism, Integrins - metabolism, Gene Expression - drug effects, DNA Primers - genetics, Cytokines - metabolism, Bronchoalveolar Lavage Fluid - cytology, Base Sequence, Antigens, Neoplasm - metabolism, Animals