title: Mast cells are an essential component of human radiation proctitis and contribute to experimental colorectal damage in mice.
abstract: Radiation proctitis is characterized by mucosal inflammation followed by adverse chronic tissue remodeling and is associated with substantial morbidity and mortality. Mast cell hyperplasia has been associated with diseases characterized by pathological tissue remodeling and fibrosis. Rectal tissue from patients treated with radiotherapy shows mast cell hyperplasia and activation, suggesting that these cells play a role in the development of radiation-induced sequelae. To investigate the role of mast cells in radiation damage, experimental radiation proctitis was induced in a mast cell-deficient (W(sh)/W(sh)) mouse model. The colon and rectum of W(sh)/W(sh) and wild-type mice were exposed to 27-Gy single-dose irradiation and studied after 2 and 14 weeks. Irradiated rodent rectum showed mast cell hyperplasia. W(sh)/W(sh) mice developed less acute and chronic rectal radiation damage than their control littermates. Tissue protection was associated with increased tissue neutrophil influx and expression of several inflammatory mediators immediately after radiation exposure. It was further demonstrated that mast cell chymase, tryptase, and histamine could change human muscularis propria smooth muscle cells into a migrating/proliferating and proinflammatory phenotype. These data show that mast cells have deleterious effects on both acute and chronic radiation proctitis, possibly by limiting acute tissue neutrophil influx and by favoring phenotypic orientation of smooth muscle cells, thus making them active participants in the radiation-induced inflammatory process and dystrophy of the rectal wall.
authors.affiliation: Laboratory of Radiopathology and Experimental Therapeutics, Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-roses, France.
authors.forename: Karl
authors.initials: K
authors.lastname: Blirando
authors.forename: Fabien
authors.initials: F
authors.lastname: Milliat
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martelly
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Agnès
authors.initials: A
authors.lastname: François
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D053818:Chymases / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D011349:Proctitis / Q000209:etiology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects*; D012007:Rectum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013194:Staining and Labeling; D053802:Tryptases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D006632:Histamine; D053818:Chymases; D053802:Tryptases