Key role of mast cells and their major secretory products in inflammatory bowel disease

Historically,mast cells were known as a key cell type involvedin type I hypersensitivity.Until last two decades,this celltype was recognized to be widely involved in a number ofnon-allergic diseases including inflammatory bowel disease(IBD).Markedly increased numbers of mast cells wereobserved in the mucosa of the ileum and colon of patientswith IBD,which was accompanied by great changes of thecontent in mast cells such as dramatically increased expressionof TNFα,IL-16 and substance P.The evidence of mast celldegranulation was found in the wall of intestine from patientswith IBD with immunohistochemistry technique.The highlyelevated histamine and tryptase levels were detected inmucosa of patients with IBD,strongly suggesting that mastcell degranulation is involved in the pathogenesis of IBD.However,little is known of the actions of histamine,tryptase,chymase and carboxypeptidase in IBD.Over the last decade,heparin has been used to treat IBD in clinical practice.Thelow molecular weight heparin(LMWH)was effective asadjuvant therapy,and the patients showed good clinical andlaboratory response with no serious adverse effects.The rolesof PGD2,LTC4,PAF and mast cell cytokines in IBD were alsodiscussed.Recently,a series of experiments with dispersedcolon mast cells suggested there should be at least twopathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner.The hypothesis is that mast cell secretogogues induce mastcell degranulation,release histamine,then stimulate theadjacent mast cells or positively feedback to further stimulateits host mast cells through H_1 receptor.Whereas releasedtryptase acts similarly to histamine,but activates mast cellsthrough its receptor PAR-2.The connections between currentanti-IBD therapies or potential therapies for IBD with mastcells were discussed,implicating further that mast cell is akey cell type that is involved in the pathogenesis of IBD.Inconclusion,while pathogenesis of IBD remains unclear,thekey role of mast cells in this group of diseases demonstratedin the current review implicates strongly that IBD is a mastcell associated disease.Therefore,close attentions should bepaid to the role of mast cells in IBD.