Effects of airway distension on leukocyte recruitment in the mouse tracheal microvasculature

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.