Role of Bone Marrow-Derived Monocytes/Macrophages in the Repair of Mucosal Damage Caused by Irradiation and/or Anticancer Drugs in Colitis Model

Junji Takaba,Kiyohiko Hatake,Yuji Mishima,Tadashi Kasahara

doi:10.1155/2010/634145

Junji Takaba, Kiyohiko Hatake + Show 2 more

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https://doi.org/10.1155/2010/634145

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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.

Highlights

Mucosal damage is a common side effect of many cancer treatments, especially intensive chemotherapy and radiotherapy
Our results suggest that monocytes/macrophages contribute to the mucosal recovery and regeneration following mucosal damage by anticancer drug therapy
white blood cells (WBCs) number decreased after Total Body Irradiation (TBI), and the low value continued around day 5. (b) Platelets number decreased, and the lowest number was observed around day 10

Summary

Introduction

Mucosal damage is a common side effect of many cancer treatments, especially intensive chemotherapy and radiotherapy This mucosal damage can seriously affect the quality of life of patients seriously and may sometimes demand changes in or limit the therapy [1,2,3]. The nuclear factor-kappa B [6], the cyclooxygenase pathway [7], and epigenetic aberrations [8] have been implicated in the regulation of radiation-induced mucositis. These findings have lead to further research into the protection and rescue of the intestinal mucosal damages in using the experimental animals. Whether these cytokines play a key role in the development and healing of radiotherapy-induced gastrointestinal mucositis remains unknown

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