title: Adherent neutrophils mediate permeability after atelectasis.
abstract: Re-expansion of atelectatic lung is associated with increased permeability. This study tests whether neutrophils mediate this event. Right middle lobar atelectasis was induced in anesthesized rabbits (n = 18) by intraluminal obstruction of the bronchus after a 20-minute ventilation with 100% O2. After 1 hour of bronchial obstruction and 20 minutes after lobar re-expansion, leukopenia was noted, 2870 +/- 210 white blood cells (WBC)/mm3, relative to control animals treated with a noninflated balloon catheter, 6500 +/- 410 WBC/mm3 (p less than 0.05). Three hours after re-expansion, neutrophils were sequestered in the previously atelectatic region 78 +/- 7 polymorphonuclear leukocytes (PMN)/10 high-power field (HPF), as well as in nonatelectatic areas, 40 +/- 3 PMN/10 HPF, higher than control values of 26 +/- 3 PMN/10 HPF (p less than 0.05). In the atelectatic region, neutrophil sequestration was associated with increased protein concentration in lobar bronchoalveolar lavage (BAL) of 1370 +/- 100 micrograms/mL, higher than control values of 270 +/- 20 micrograms/mL (p less than 0.05). Reexpansion also induced increases in lung wet-to-dry weight ratio (W/d) of 6.2 +/- 0.2, higher than control values of 4.3 +/- 0.1 (p less than 0.05). Rendering rabbits neutropenic (n = 18) (0 to 4 PMN/mm3) limited the atelectasis-induced protein accumulations in BAL (520 +/- 60 micrograms/mL) and increase in lung W/d (5.2 +/- 0.1) (both p less than 0.05). Intravenous (I.V.; treatment of another group (n = 18) with an anti-CD 18 monoclonal antibody (R 15.7, 1 mg/kg) before balloon deflation prevented leukopenia (6550 +/- 560 WBC/mm3), minimized neutrophil sequestration (36 +/- 2 PMN/10 HPF), and attenuated protein leak (710 +/- 95 micrograms/mL) and the increased lung W/d (5.6 +/- 0.1) (all p less than 0.05). A final atelectatic group (n = 9) was treated I.V. with the anti-intercellular adhesion molecule-1 monoclonal antibody (RR 1/1, 1 mg/kg), which also prevented leukopenia and showed similar protection of microvascular barrier function. These data indicate that adherent neutrophils in large part mediate lung permeability and edema after atelectasis and re-expansion. Adhesion receptors of both neutrophils and endothelial cells regulate this event.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: G
authors.initials: G
authors.lastname: Goldman
authors.forename: R
authors.initials: R
authors.lastname: Welbourn
authors.forename: R
authors.initials: R
authors.lastname: Rothlein
authors.forename: M
authors.initials: M
authors.lastname: Wiles
authors.forename: L
authors.initials: L
authors.lastname: Kobzik
authors.forename: C R
authors.initials: CR
authors.lastname: Valeri
authors.forename: D
authors.initials: D
authors.lastname: Shepro
authors.forename: H B
authors.initials: HB
authors.lastname: Hechtman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001998:Bronchopulmonary Sequestration / Q000503:physiopathology; D002448:Cell Adhesion; D007970:Leukopenia / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010539:Permeability; D011506:Proteins / Q000032:analysis; D001261:Pulmonary Atelectasis / Q000209:etiology* / Q000503:physiopathology; D011817:Rabbits
chemical_list: D000911:Antibodies, Monoclonal; D011506:Proteins