Inhibition of inflammatory liver injury by a monoclonal antibody against lymphocyte function-associated antigen-1.
When mice were given an i.v. injection of LPS 7 days after an i.v. injection of Propionibacterium acnes, liver injury and a rapid increase of serum alanine aminotransferase and asparagine acid aminotransferase occurred. The in vivo administration of mAb against LFA-1 on days 1, 2, and 3 after the i.v. injection of P. acnes resulted in a potent inhibition of all these dysfunctions. Using P. acnes and the LPS model, we found that anti-LFA-1 mAb protected the mice from P. acnes and LPS-induced lethal shock. During the course of P. acnes and LPS-induced liver injury, inflammatory cells infiltrated the liver and caused a massive hepatic cell necrosis. Flow cytometry revealed that the liver-infiltrating cells were mainly leukocytes expressing a higher level of LFA-1 antigen than that seen in the normal liver. These results suggested that the LFA-1 molecule on liver-infiltrating leukocytes may play an important role in the induction of inflammatory liver injury.
Tanaka
Y
Y
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Ohmiya, Japan.
Kobayashi
K
K
Takahashi
A
A
Arai
I
I
Higuchi
S
S
Otomo
S
S
Habu
S
S
Nishimura
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D006520:Hepatitis, Animal / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007962:Leukocytes / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011233:Precipitin Tests; D012772:Shock, Septic / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase