Effects of VLA-1 Blockade on Experimental Inflammation in Mice

Kobe J Med Sci. 2016 Jul 5;62(2):E27-37.

Abstract

VLA-1 (very late antigen-1) is implicated in recruitment, retention and activation of leukocytes and its blockade has been referred as a potential target of new drug discovery to address unmet medical needs in inflammatory disease area. In the present study, we investigate the effects of an anti-murine CD49a (integrin α subunit of VLA-1) monoclonal antibody (Ha31/8) on various experimental models of inflammatory diseases in mice. Pretreatment with Ha31/8 at an intraperitoneal dose of 250 µg significantly (P<0.01) reduced arthritic symptoms and joint tissue damage in mice with type II collagen-induced arthritis. In addition, Ha31/8 at an intraperitoneal dose of 100 µg significantly (P<0.01) inhibited airway inflammatory cell infiltration induced by repeated exposure to cigarette smoke. In contrast, Ha31/8 failed to inhibit oxazolone-induced chronic dermatitis and OVA-induced airway hyperresponsiveness at an intraperitoneal dose of 100 µg. These results show that VLA-1 is involved, at least partly, in the pathogenesis of type II collagen-induced arthritis and cigarette smoke-induced airway inflammatory cell infiltration in mice, indicating the therapeutic potential of VLA-1 blockade against rheumatoid arthritis and chronic occlusive pulmonary disease.

Keywords: Airway inflammation; Arthritis; Dermatitis; Ha31/8; Inflammation; VLA-1.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / prevention & control
  • Asthma / immunology
  • Asthma / prevention & control
  • Dermatitis / immunology
  • Dermatitis / prevention & control
  • Disease Models, Animal
  • Female
  • Inflammation / immunology
  • Inflammation / prevention & control*
  • Integrin alpha1beta1 / antagonists & inhibitors*
  • Integrin alpha1beta1 / immunology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Pneumonia / etiology
  • Pneumonia / immunology
  • Pneumonia / prevention & control
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / prevention & control
  • Smoking / adverse effects

Substances

  • Antibodies, Monoclonal
  • Integrin alpha1beta1