Lay Summary

Proposal No.   IBD-0066
Principal Investigator:  Judith Bond, Ph.D. (replacement PI);  Jacqueline Crisman, Ph.D. (original PI)
Applicant Organization:  The Pennsylvania State University College of Medicine (Hershey, U.S.A.)
Project Title: Intestinal leukocyte infiltration is mediated by meprin beta
Period of Award:  June 1, 2003 - July 31, 2004

Research has indicated that the movement of white blood cells into the intestine is one of the pivotal events leading to inflammatory bowel disease (IBD).  White blood cells are normally thought to assist in preventing disease.  However, in many types of inflammation, these cells can emit proteins that exacerbate disease.  Thus, the means by which white blood cells enter the intestine and associated tissues is a very active area of research, in hopes of targeting these mechanisms clinically.

We will examine the role of the enzyme meprin β in intestinal leukocyte infiltration.  Current evidence indicates that meprin β is pivotal to the movement of white blood cells into the intestinal immune system.  To test this hypothesis, white blood cells will be isolated from mice that do not carry the gene for meprin β (so-called meprin β null mice) and wild-type mice (that carry the meprin β gene).  These two types of white blood cells will be labeled and injected into mice, so their deposition can be followed into the intestine and associated lymphatic tissue.  These experiments will be performed under normal or inflammatory conditions, which simulate IBD.
 
The role of proteases in the movement of white blood cells into tissue is not well understood.  We will establish the role of meprin b metalloprotease in the deposition of white blood cells into the intestine.  Thus, blocking meprin b activity may be used as a novel means of treatment for IBD, without affecting the normal immune responses found in other tissues.