The anti Mac-1 monoclonal antibody inhibits neutrophil sequestration in lung and liver in a septic murine model.
We investigated the mechanism by which leukocytes adhere to the pulmonary and liver microvascular endothelium in a septic murine model. After C57BL/6 mice were intraperitoneally (ip) injected with lipopolysaccharide (LPS), a striking peripheral leukocytopenia occurred as neutrophils accumulated rapidly in the lung and liver. When the anti-Mac-1 monoclonal antibody (mAb) was administered intravenously (iv) 2 hr before the ip administrated LPS, leukocytopenia and neutrophil accumulation in the lung and liver were inhibited significantly at 3 hr after the LPS injection. An immunofluorescence study revealed that Mac-1 expression on leukocytes from LPS-injected mice were greatly increased when compared to that of controls. Additionally, an in vitro assay demonstrated that LPS-activated serum increased neutrophil Mac-1 expression and neutrophil adhesion to the endothelial monolayer and that these phenomena are inhibited by pretreatment of neutrophils with anti-Mac-1 mAb. These results indicate that a marked increase in Mac-1 antigen expression by leukocytes plays a crucial role in striking neutrophil attachment to the vascular endothelium and is likely to be the cause of neutrophil accumulation in the lung and liver during endotoxemia.
First Department of Surgery, Kyushu University School of Medicine, Fukuoka, Japan.
T
T
Morisaki
T
T
Goya
H
H
Toh
K
K
Nishihara
M
M
Torisu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D004731:Endotoxins / Q000097:blood*; D006801:Humans; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen