Expression of integrin alpha v beta 6 in rats with ventilator-induced lung injury and the attenuating effect of synthesized peptide S247.
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.
Wu
Qingping
Q
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. wu_qingping1968@yahoo.com.cn
Gui
Ping
P
Yao
Shanglong
S
Xiang
Huiyun
H
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
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