title: Murine mechanical ventilation stimulates alveolar epithelial cell proliferation.
abstract: High tidal volume mechanical ventilation can cause inflammation and lung damage. Mechanical strain is also necessary for normal lung growth. The current work was performed to determine if mechanical ventilation with clinically utilized tidal volumes stimulates a proliferative response in the lung. Six- to 8-week-old C57/Bl6 mice, anesthetized with ketamine/xylozine, were ventilated for 6 hours with 10 mL/kg tidal volume, positive end-expiratory pressure (PEEP) 3cm H(2)O. Pulmonary function testing demonstrated decreased compliance within 3 hours of ventilation. Assessment of bronchoalveolar lavage (BAL) demonstrated no significant increase in lactate dehydrogenase, total lavagable cell number, or total protein after ventilation. There was evidence of inflammation in the lungs of ventilated mice, with an increased percentage of lymphocytes and neutrophils in BAL, and an increase in macrophage inflammatory protein (MIP)-2 and interleukin (IL)-1beta message in lung tissue. Immunohistochemistry of inflation-fixed lungs demonstrated increased alveolar cell proliferation, as measured by both proliferating cell nuclear antigen and Ki67 staining. Dual staining confirmed that proliferating cells labeled with proSP-B, demonstrating that ventilation induces proliferation of alveolar type II cells. Ventilation did not increase apoptosis in alveolar type II cells, as measured by TUNEL staining. Ventilation at low tidal volumes leads to a mild inflammatory response and alveolar epithelial cell proliferation.
authors.affiliation: Departments of Pediatrics and Biomedical Engineering, University of Rochester, Rochester, New York 14642, USA. patricia chess@urmc.rochester.edu
authors.forename: Patricia Rose
authors.initials: PR
authors.lastname: Chess
authors.forename: Randi Potter
authors.initials: RP
authors.lastname: Benson
authors.forename: William M
authors.initials: WM
authors.lastname: Maniscalco
authors.forename: Terry W
authors.initials: TW
authors.lastname: Wright
authors.forename: Michael A
authors.initials: MA
authors.lastname: O'Reilly
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Johnston
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D054426:Chemokine CXCL2 / Q000235:genetics; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D019394:Ki-67 Antigen / Q000378:metabolism; D008170:Lung Compliance; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000209:etiology / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology*; D013990:Tidal Volume; D013997:Time Factors; D055397:Ventilator-Induced Lung Injury / Q000209:etiology / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D011498:Protein Precursors; D011510:Proteolipids; C105511:surfactant protein B propeptide