PURPOSE: Our previous study reveals bone marrow transplantation (BMT) recruits host marrow-derived myelomonocytic cells to radiation-injured intestine, enhancing stromal proliferation, leading secondarily to epithelial regeneration. In this study, we propose BMT ameliorates intestinal damage via paracrine mechanisms. MATERIALS AND METHODS: Angiogenic cytokines within the intestinal mucosa of mice after whole body irradiation (WBI) with or without BMT were measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused into mice for three days after radiation. Carrageenan was used to deplete myelomonocytic cells of mice. RESULTS: BMT increased VEGF, bFGF and other angiogenic and chemotactic cytokines in the intestinal mucosa within 24h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage with improved stromal activity and prolonged survival of mice. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to the intestine. Pretreatment of carrageenan to recipient mice reversed some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal mucosa after BMT. CONCLUSIONS: Our result suggests BMT recruits host myelomonocytic cells and enhances intestinal stroma proliferation after radiation by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic cells further uplift the paracrine effect to enhance intestinal mucosal recovery.
PURPOSE: Our previous study reveals bone marrow transplantation (BMT) recruits host marrow-derived myelomonocytic cells to radiation-injured intestine, enhancing stromal proliferation, leading secondarily to epithelial regeneration. In this study, we propose BMT ameliorates intestinal damage via paracrine mechanisms. MATERIALS AND METHODS: Angiogenic cytokines within the intestinal mucosa of mice after whole body irradiation (WBI) with or without BMT were measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused into mice for three days after radiation. Carrageenan was used to deplete myelomonocytic cells of mice. RESULTS: BMT increased VEGF, bFGF and other angiogenic and chemotactic cytokines in the intestinal mucosa within 24h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage with improved stromal activity and prolonged survival of mice. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to the intestine. Pretreatment of carrageenan to recipient mice reversed some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal mucosa after BMT. CONCLUSIONS: Our result suggests BMT recruits host myelomonocytic cells and enhances intestinal stroma proliferation after radiation by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic cells further uplift the paracrine effect to enhance intestinal mucosal recovery.
Authors: Andrea L DiCarlo; Radia Tamarat; Carmen I Rios; Marc Benderitter; Christine W Czarniecki; Theresa C Allio; Francesca Macchiarini; Bert W Maidment; Jean-Rene Jourdain Journal: Radiat Res Date: 2017-06-12 Impact factor: 2.841
Authors: Liang Wei; Brian J Leibowitz; Michael Epperly; Cheng Bi; Allen Li; Justin Steinman; Peter Wipf; Song Li; Lin Zhang; Joel Greenberger; Jian Yu Journal: Sci Rep Date: 2018-02-01 Impact factor: 4.379