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

R. Cartland Burns, Jesus Rivera-Nieves, Christopher A. Moskaluk, Satoshi Matsumoto, Fabio Cominelli, Klaus Ley

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Background & Aims: Integrins (α4 and β2) 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 α4 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 α4, or both ICAM-1 and α4, 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 α4 integrins had no significant beneficial effect. However, blocking ICAM-1 and α4, 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.

Original languageEnglish
Pages (from-to)1428-1436
Number of pages9
JournalGastroenterology
Volume121
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Dive into the research topics of 'Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1/Yit adoptive transfer model of Crohn's disease in mice'. Together they form a unique fingerprint.

Cite this