title: Role of bone marrow-derived monocytes/macrophages in the repair of mucosal damage caused by irradiation and/or anticancer drugs in colitis model.
abstract: Mucosal damage is a common side effect of many cancer treatments, especially radiotherapy and intensive chemotherapy, which often induce bone marrow (BM) suppression. We observed that acetic acid- (AA-) induced mucosal damage in the colon of mice was worsened by simultaneous treatment with irradiation or 5-FU. However, irradiation 14 days prior to the AA treatment augmented the recovery from mucosal damage, suggesting that the recovery from BM suppression had an advantageous effect on the mucosal repair. In addition, BM transplantation also augmented the recovery from AA-induced mucosal damage. We further confirmed that transplanted BM-derived cells, particularly F4/80+Gr1+ "inflammatory" monocytes (Subset 1), accumulated in the damaged mucosal area in the early healing phase, and both of Subset 1 and F4/80+Gr1⁻ "resident" monocytes (Subset 2) accumulated in this area in later phases. Our results suggest that monocytes/macrophages contribute to the mucosal recovery and regeneration following mucosal damage by anticancer drug therapy.
authors.affiliation: Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Takaba
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishima
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D011878:Radiotherapy / Q000009:adverse effects*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D015415:Biomarkers; D007202:Indicators and Reagents; D019342:Acetic Acid; D005472:Fluorouracil