Modulation by pentobarbital of neutrophil responses to inhaled E-coli endotoxin in sheep: role of lung epithelium

Neutrophils (PMNs) are implicated in the pathogenesis of acute respiratory distress syndrome (ARDS), The role of the epithelium in the modulation of P MN migration within the lungs was examined, Epithelial integrity and PMN concentrations in the lung air spaces and lymp h were measured in sheep anaesthetized with either halothane (1-2.5%) or in travenous pentobarbital (12+/-4 mg.kg(-1).h(-1)). Ventilation with an aeros ol containing 25 mg Escherichia Coli endotoxin (lipopolysaccharide; LPS) ef fected neutrophil recruitment to the air spaces, Lymphatic clearance of aer osolized Tc-99m-DTPA provided an index of epithelial integrity. Three hours after the deposition of LPS, the lung lining fluid of sheep ana esthetized,vith halothane (n=7) had 4.9+/-3.2X10(6) PMN.mL(-1), but the lun g lymph had almost no PMNs (3+/-8%), Sheep anaesthetized with pentobarbital (n=6) had fewer PMNs in the air spaces (2.4+/-1.2X10(6).mL(-1)) and more P MNs in the lung lymph (30+/-20%). Control sheep (n=5) that received no LPS had almost no PMNs in the airspaces or lung lymph, regardless of the anaest hesia. Three additional sheep that remained awake after receiving LPS also had no PMNs in the lung lymph. The PMN fraction in the lung lymph correlate d well with the extra-alveolar epithelial permeability measured by lymphati c clearance of aerosolized diethylenetriamine penta-acetic acid (r=0.81, p< 0.001). Aerosolized lipopolysaccharide recruits neutrophils into the lungs of sheep , but they appear to remain in the airspaces unless extra-alveolar permeabi lity is increased by agents such as pentobarbital.