Neutrophil adhesion receptor CD18 mediates remote but not localized acid aspiration injury.
BACKGROUND
Acid aspiration leads to lung polymorphonuclear neutrophil (PMN) sequestration and an associated increase in permeability. Although it is known that the neutrophil adhesion receptor (CD18) plays no role in determining PMN accumulations in the region aspirated, we postulated that this PMN adhesion receptor and its endothelial ligand, intercellular adhesion molecule-1 (ICAM-1), mediate remote neutrophil sequestration.


METHODS
Anesthetized rabbits underwent localized aspiration of either 0.1N HCl 0.1 ml/kg (n = 18) or saline solution (n = 18).


RESULTS
After 30 minutes leukopenia was noted, 2290 +/- 200 white blood cells/mm3 (p < 0.05). At 3 hours diapedesis occurred in the aspirated segment with accumulations in bronchoalveolar lavage fluid (X10(4)) of 87 +/- 6 PMN/ml versus control of 6 +/- 1 PMN/ml (p < 0.05). Histologic evidence of generalized lung leukosequestration occurred. The wet to dry weight ratio of the nonaspirated lung rose to 5.7 +/- 0.2 versus control of 3.9 +/- 0.1 (p < 0.05). Treatment (n = 18) with the CD18 monoclonal antibody (mAb) (R15.7, 1 mg/kg) had no effect on neutrophil accumulations in the aspirated segment. However, the mAb attenuated the remote inflammatory response: early leukopenia (5790 +/- 400 white blood cells/mm3); lung leukosequestration (24 +/- 4 PMN/10 high-power fields); protein leak in bronchoalveolar lavage fluid (570 +/- 50 micrograms/ml); and edema, wet to dry weight ratio (4.9 +/- 0.1) (all p < 0.05). Treatment with the ICAM-1 mAb (RR1/1, 1 mg/kg) (n = 9) did not reduce neutrophil accumulations in the aspirated segment but limited the remote inflammatory response.


CONCLUSIONS
Acid aspiration leads to neutrophil adhesion and edema in regions remote from those aspirated via neutrophil CD18 and endothelial ICAM-1.
Goldman
G
G
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Welbourn
R
R
Kobzik
L
L
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007970:Leukopenia / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D011015:Pneumonia, Aspiration / Q000276:immunology*; D011817:Rabbits; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*
D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D018799:Intercellular Adhesion Molecule-1