Deletion of the mouse meprin beta metalloprotease gene diminishes the ability of leukocytes to disseminate through extracellular matrix.

Abstract

Meprins are metalloendopeptidases expressed by leukocytes in the lamina propria of the human inflamed bowel, that degrade extracellular matrix proteins in vitro implicating them in leukocyte transmigration events. The aims of these studies were to 1) examine the expression of meprins in the mouse mesenteric lymph node, 2) determine whether macrophages express meprins, and 3) determine whether deletion of the meprin beta gene (Mep-1beta) mitigated the ability of leukocytes to disseminate through extracellular matrix in vitro. These studies show that meprin alpha and beta are expressed in leukocytes of the mouse mesenteric lymph node, and meprin alpha, but not beta, decreased during intestinal inflammation. Deletion of Mep-1beta gene decreased the ability of leukocytes to migrate through matrigel compared with wild-type leukocytes. Meprin beta, but not alpha, was detected in cortical and medullary macrophages of the lymph node. Thus overall, meprin beta is expressed by leukocytes in the draining lymph node of the intestine, regardless of the inflammatory status of the animal, and is likely to contribute to leukocyte transmigration events important to intestinal immune responses. Thus, the expression of meprins by leukocytes of the intestinal immune system may have important implications for diseases such as inflammatory bowel diseases, which are aggravated by leukocyte infiltration.