Oxygen-induced lung injury in the guinea pig proceeds through CD18-independent mechanisms.

Abstract

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.

Dissociation between alveolar transmigration of neutrophils and lung injury in hyperoxia

“…However, the relative importance of these CAMs to sequential changes in cellular trafficking during prolonged O 2 exposure is still unknown. It has been suggested that PMN influx during hyperoxic exposure occurs through a predominantly CD11/ CD18-independent pathway (19,26). Keeney et al (26), using an MAb directed against the CD18 complex in adult guinea pigs, found no change in neutrophil influx or lung injury after 72 h of hyperoxia, suggesting a predominantly CD18-independent pathway for emigration.…”

The Role of Angiopoietin 2 in Hyperoxia-Inuduced Acute Lung Injury

“…7 In contrast, hyperoxia can induce ALI in animal models that lack leukocytes. [28][29][30][31] This dissociation demonstrates that HALI-induced tissue injury cannot be attributed solely to local tissue inflammation.…”

Unique Structural Features That Influence Neutrophil Emigration Into the Lung

“…Doerschuk et al (54) demonstrated a number of years ago that this process can occur through at least two distinct pathways. One pathway reguires ␤ 2 -integrins, whereas the other does not, and the distinction depends on the stimulus (54,96,126,137,180,185,203,205,234). There is also evidence from studies in the peritoneal cavity that macrophages are essential for production of a stimulus that elicits ␤ 2 -integrin-independent neutrophil emigration (173).…”