Oxygen-induced lung injury in the guinea pig proceeds through CD18-independent mechanisms.
The pathogenesis of pulmonary oxygen toxicity is postulated to be related in part to neutrophil-mediated injury. This study examined the effect of a monoclonal antibody directed against the CD11a,b,c/CD18 glycoprotein complex (beta 2 leukocyte integrins) on oxygen-induced lung injury. M8, a monoclonal antibody that binds to the beta chain of the guinea pig leukocyte integrins that facilitate neutrophil adherence to vascular endothelium, was injected into adult guinea pigs prior to and during exposure to > 98% oxygen. Control oxygen-exposed animals were injected with a noninhibitory antibody to the CD18 complex or with saline. Survival in oxygen was similar for animals treated with M8 when compared with those treated with saline (102 versus 105 h, respectively, NS). Pulmonary edema as assessed by protein in the supernatant of bronchoalveolar lavage fluid (BALF) was higher in the three groups of oxygen-exposed animals than in the air-exposed groups (p < 0.01), but it did not differ between the M8 antibody treatment group and the other oxygen-exposed groups. M8 antibody treatment did not decrease hyperoxia-induced neutrophil accumulation into the lung as assessed by myeloperoxidase activity (MPO) in lung homogenates or by neutrophil counts in histologic specimens. M8 antibody also did not decrease neutrophil counts or MPO in alveolar lavage fluid, both of which were significantly elevated in all oxygen-exposed groups. These results suggest that hyperoxia-induced neutrophil migration into the lung and acute lung injury occurs by CD18-independent processes in the guinea pig model of pulmonary oxygen toxicity.
Keeney
S E
SE
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555.
Mathews
M J
MJ
Haque
A K
AK
Rudloff
H E
HE
Schmalstieg
F C
FC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D005434:Flow Cytometry; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010100:Oxygen / Q000009:adverse effects*; D011654:Pulmonary Edema / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D010100:Oxygen