Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1/Yit adoptive transfer model of Crohn's disease in mice

Gastroenterology. 2001 Dec;121(6):1428-36. doi: 10.1053/gast.2001.29568.


Background & aims: Integrins (alpha(4) and beta(2)) and their endothelial ligands vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) play key roles in leukocyte recruitment to areas of inflammation. ICAM-1 and VCAM-1 are expressed in inflamed intestinal tissues. This study investigates a possible causative role of adhesion molecules ICAM-1, VCAM-1, and alpha(4) integrins in mediating the inflammatory response in a murine model of Crohn's disease (CD).

Methods: CD4+ mesenteric lymph node cells from SAMP-1/Yit donor mice were adoptively transferred into major histocompatibility complex-matched severe combined immunodeficiency disease mice. Six weeks later, these mice were left untreated or treated for 3 days with monoclonal antibodies (mAbs) to ICAM-1, VCAM-1, or both, and alpha(4), or both ICAM-1 and alpha(4), dexamethasone, or nonblocking isotype control antibodies. On day 4 after treatment, tissues were investigated for expression of ICAM-1, VCAM-1, and for severity of inflammation using a semiquantitative inflammatory score. Dexamethasone treatment resolved all measures of intestinal inflammation.

Results: Blocking either ICAM-1, VCAM-1, or alpha(4) integrins had no significant beneficial effect. However, blocking ICAM-1 and alpha(4), or blocking ICAM-1 and VCAM-1, showed a 70% resolution of the active inflammation, but not chronic inflammation.

Conclusions: These findings suggest that blocking ICAM-1 and VCAM-1 may have therapeutic benefit for the acute inflammatory component of Crohn's disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigens, CD / immunology
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / metabolism*
  • Colon / pathology*
  • Crohn Disease / immunology
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / immunology
  • Integrin alpha4
  • Intercellular Adhesion Molecule-1 / immunology*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mice, SCID
  • Microvilli / pathology
  • Vascular Cell Adhesion Molecule-1 / immunology*
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Antibodies, Monoclonal
  • Antigens, CD
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Integrin alpha4