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.
Morisaki
T
T
First Department of Surgery, Kyushu University School of Medicine, Fukuoka, Japan.
Goya
T
T
Toh
H
H
Nishihara
K
K
Torisu
M
M
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