title: Expression of integrin alpha v beta 6 in rats with ventilator-induced lung injury and the attenuating effect of synthesized peptide S247.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. wu_qingping1968@yahoo.com.cn
authors.forename: Qingping
authors.initials: Q
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Gui
authors.forename: Shanglong
authors.initials: S
authors.lastname: Yao
authors.forename: Huiyun
authors.initials: H
authors.lastname: Xiang
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury; D008297:Male; D009842:Oligopeptides / Q000819:agonists; D009930:Organic Chemicals / Q000138:chemical synthesis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D017931:DNA Primers; D016023:Integrins; D009842:Oligopeptides; D009930:Organic Chemicals; D012333:RNA, Messenger; C474314:S 247 compound; C073878:integrin alphavbeta6; C047981:arginyl-glycyl-aspartic acid