title: Effects of airway distension on leukocyte recruitment in the mouse tracheal microvasculature.
abstract: We have shown previously that excessive distention of the rat trachea during mechanical ventilation results in enhanced leukocyte recruitment to the airway (Lim LH and Wagner EM. Am J Respir Crit Care Med 168:1068-1074, 2003). The objectives of this study were to develop a mouse model of positive end-expiratory pressure (PEEP)-induced leukocyte recruitment to the airway and begin to pursue molecular mechanisms that may contribute to the in vivo observation of increased leukocyte adhesion after PEEP exposure. We studied C57BL/6 wild-type mice and mice deficient in P-selectin or intercellular adhesion molecule-1 (ICAM-1) exposed to intermittent PEEP (8 cmH(2)O) applied five times for a 1-min duration, at 10-min intervals. After the imposed ventilatory stress, during normal ventilation (0.2 ml/breath, no PEEP), leukocyte adhesion in tracheal postcapillary venules was determined using intravital microscopy. PEEP induced a time-dependent increase in leukocyte adhesion that was significantly increased between 0 and 60 min (P < 0.01). Furthermore, PEEP-induced leukocyte adhesion at 60 min was ablated in P-selectin- and ICAM-1-deficient mice. These findings demonstrate the essential nature of both P-selectin and ICAM-1 within airway postcapillary venular endothelium for leukocyte recruitment after airway distension.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21224, USA. wagnerem@jhmi.edu
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Wagner
authors.forename: John
authors.initials: J
authors.lastname: Jenkins
mesh_terms: D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology*; D011175:Positive-Pressure Respiration / Q000379:methods*; D013314:Stress, Mechanical; D014132:Trachea / Q000098:blood supply* / Q000502:physiology*
chemical_list: D018799:Intercellular Adhesion Molecule-1