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

Abstract

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.

• Authors: R C Burns, J Rivera-Nieves, C A Moskaluk, S Matsumoto, F Cominelli, K Ley
• Journal: Gastroenterology (Gastroenterology) Vol. 121 Issue 6 Pg. 1428-36 (Dec 2001) ISSN: 0016-5085 [Print] United States
• PMID: 11729122 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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