Renoprotective role of interstitial macrophages in the evolution of renal fibrosis

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We performed adoptive transfer of bone marrow-derived(BM) macrophages following pharmacological depletion of leukocytes in a mouse model of unilateral ureteral obstruction(UUO), a well-established experimental model of progressive renal interstitial fibrosis. Treatment with cyclophosphamide(CPM) caused marked decrease in the numbers of F4/80-positive interstitial macrophages as well as in peripheral blood leukocyte counts, and adoptive transfer of BM macrophages to CPM-treated mice resulted in significant increase in the numbers of interstitial macrophages both at day 5 and at day 14 after UUO. At day 5 after UUO, no significant change was observed in the degree of renal interstitial fibrosis either by treatment with CPM or with CPM+macrophage. However, at day 14 after UUO, treatment with CPM caused significant increase in the degree of interstitial fibrosis, and adoptive macrophage transfer to these mice attenuated this enhancement in renal fibrosis. Our result suggests the role of infiltrating macrophages on facilitating tissue repair at late stage of UUO.