title: Modulatory effects of hypercapnia on in vitro and in vivo pulmonary endothelial-neutrophil adhesive responses during inflammation.
abstract: Reducing tidal volume as a part of a protective ventilation strategy may result in hypercapnia. In this study, we focused on the influence of hypercapnia on endothelial-neutrophil responses in models of inflammatory-stimulated human pulmonary microvascular endothelial cells (HMVEC) and in an animal model of lipopolysaccharide (LPS)-induced acute lung injury. Neutrophil adhesion and adhesion molecules expression and nuclear factor-kappaB (NF-kappaB) were analyzed in TNF-alpha and LPS-treated HMVEC exposed to either eucapnia or hypercapnia. In the in vivo limb, bronchoalveolar lavage fluid cell counts and differentials, adhesion molecule and chemokine expression were assessed in LPS-treated rabbits ventilated with either low tidal volume ventilation and eucapnia or hypercapnia. In both the in vitro and in vivo models, hypercapnia significantly increased neutrophil adhesion and adhesion molecule expression compared to eucapnia. Activity of NF-kappaB was significantly enhanced by hypercapnia in the in vitro experiments. IL-8 expression was greatest both in vitro and in vivo under conditions of hypercapnia and concomitant inflammation. CD11a expression was greatest in isolated human neutrophils exposed to hypercapnia+LPS. Our results demonstrate that endothelial-neutrophil responses per measurement of fundamental molecules of adhesion are significantly increased during hypercapnia and that hypercapnia mimics conditions of eucapnia+inflammation.
authors: Department of Anesthesiology, VA Puget Sound Health Care System, University of Washington School of Medicine, 1660 South Columbian Way, Seattle, WA 98108-1597, USA. yuliang6@u.washington.edu
authors: Yuliang
authors: Y
authors: Liu
authors: Balu K
authors: BK
authors: Chacko
authors: Ana
authors: A
authors: Ricksecker
authors: Roman
authors: R
authors: Shingarev
authors: Eric
authors: E
authors: Andrews
authors: Rakesh P
authors: RP
authors: Patel
authors: John D
authors: JD
authors: Lang
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D007249:Inflammation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000096:biosynthesis; D011817:Rabbits; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016209:Interleukin-8; D008070:Lipopolysaccharides; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1