Bone marrow-derived macrophages are associated with androgen modulated prostate regeneration.

BACKGROUND

Recent studies have reported that bone marrow-derived cells (BMDCs) can be cellular components of tissue undergoing remodeling. However, the types of BMDCs that contribute to prostate regeneration are unclear. Elucidating the association between BMDCs and prostate regeneration will help to identify the mechanism responsible for abnormal prostate tissue remodeling in conditions such as benign prostate hyperplasia, proliferative inflammatory atrophy, and prostate cancer.

METHODS

We used a bone marrow transplantation (BMT) technique involving green fluorescent protein (GFP)-expressing bone marrow cells and a murine model of prostate regeneration induced by androgen modulation. Immunophenotypes of recruited GFP-positive cells at days 3, 14, and 28 after regeneration were analyzed in the prostate tissue of mice that had undergone BMT.

RESULTS

During the regenerating process, the most abundant BMDC phenotype was the F4/80-positive macrophage followed by the CD3-positive T lymphocyte. The proportion of all nucleated cells that were F4/80-positive BMDCs was greatest at day 3 after regeneration and was lower at days 14 and 28. By contrast, the proportion of F4/80-positive/GFP-negative cells remained unchanged at days 3, 14, and 28. Macrophage-colony stimulating factor mRNA expression level was the highest in the regenerating prostate. The number of F4/80-positive BMDCs, but not CD3-positive BMDCs, correlated with the proliferative activity of epithelial cells of the regenerating prostate at day 14.

CONCLUSIONS

The observation that bone marrow-derived macrophages are recruited into the prostate where they associate with prostate regeneration suggests that bone marrow-derived macrophages are involved in prostate regeneration.