Along its length, the intestine is lined by a soft and delicate mucosal layer, -1 mm thick, but 400 m2 in area.
The mucosa is a highly vascular, loose connective-tissue matrix containing structural collagens, glycoproteins such as laminin and fibronectin, chondroitin sulphate proteoglycans such as versican, hyaluronic acid, and ground substance. These are secreted by lamina propria stromal cells (also known as myofibroblasts or mesenchymal cells), and where the stromal cells abut the epithelium and endothelium, there is synergy between the two cell types to construct the basement membrane, containing laminin, heparan sulphate proteoglycans, entactin, and collagen IV. Of all the tissues in the body, the intestinal lamina propria is the most plastic and the one in which extracellular matrix degradation and repair must be tightly controlled. For example, whereas matrix degradation in the rheumatoid joint causes pain, deformity, and disability, matrix degradation in the gut leads to ulceration, diarrhea, malabsorption, and protein-losing enteropathy .
Inflammatory cells such as neutrophils, macrophages, eosinophils, and mast cells are increased in numbers in the mucoqa in inflammatory bowel disease (IBD). Although there is a great deal of interest in the cytokines and toxic molecules produced by these cells, they are also a rich source of proteolytic enzymes, such as the serine protease neutrophil elastase, and various acidic cysteine proteases. In addition, endogenous fibroblastlike stromal cells are a potent source of matrix metalloproteinases (MMPs). Although in health, stromal cells secrete matrix and low amounts MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) as part of nor-Address correapondence and reprint requests to Dr.