The role of leukocyte emigration and IL-8 on the development of lipopolysaccharide-induced lung injury in rabbits.
Leukocyte emigration and alveolar macrophage-derived cytokines may contribute to lung microvascular injury associated with adult respiratory distress syndrome. We have used mAbs against cell adhesion molecules on leukocytes (anti-CD18 and anti-CD49d) or against IL-8 to investigate these contributions. Intratracheal (i.t.) instillation of LPS (50 microg/kg) caused a significant increase in bronchoalveolar lavage polymorphonuclear leukocytes (PMNs) without an increase in mononuclear cells (MNCs) or an increase in lung permeability. Injection of LPS (10 microg/kg) i.v. at 24 h after i.t. LPS caused significant increases in bronchoalveolar lavage PMNs, MNCs, IL-8, and monocyte chemotactic protein-1, as well as increases in lung permeability. Rabbits that were administered i.t. LPS followed by i.v. LPS and treated with anti-CD18 mAb had a significantly lower lung permeability index and emigration of fewer PMNs but no change in MNC emigration compared with saline treatment. Anti-IL-8 mAb treatment resulted in a significantly lower lung permeability index with no change in PMN emigration compared with no treatment. These results suggest that PMN emigration is necessary but not sufficient for the development of LPS-induced lung injury, and that IL-8 plays a significant role in PMN-dependent lung injury, independent of PMN emigration.
Yamamoto
T
T
Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation, Japan.
Kajikawa
O
O
Martin
T R
TR
Sharar
S R
SR
Harlan
J M
JM
Winn
R K
RK
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007275:Injections, Intravenous; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007442:Intubation, Intratracheal; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000276:immunology / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides