Role of bone marrow-derived monocytes/macrophages in the repair of mucosal damage caused by irradiation and/or anticancer drugs in colitis model

Mediators Inflamm. 2010:2010:634145. doi: 10.1155/2010/634145. Epub 2011 Jan 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / pharmacology
  • Animals
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents / adverse effects*
  • Biomarkers
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism*
  • Bone Marrow Cells / radiation effects
  • Colitis / chemically induced
  • Colitis / pathology*
  • Disease Models, Animal
  • Fluorouracil / pharmacology
  • Humans
  • Indicators and Reagents / pharmacology
  • Intestinal Mucosa* / drug effects
  • Intestinal Mucosa* / pathology
  • Intestinal Mucosa* / radiation effects
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / radiation effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Monocytes / radiation effects
  • Radiotherapy / adverse effects*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Biomarkers
  • Indicators and Reagents
  • Acetic Acid
  • Fluorouracil