Bone Marrow Transplantation Helps Restore the Intestinal Mucosal Barrier after Total Body Irradiation in Mice
Bone marrow transplantation (BMT) substantially improves 10-day survival after total body irradiation (TBI), consistent with an effect on intestinal radiation death. Total body irradiation, in addition to injuring the intestinal epithelium, also perturbs the mucosal immune system, the largest immune...
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| Veröffentlicht in: | Radiation research 2014-03, Vol.181 (3), p.229-239 |
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| creator | Garg, Sarita Wang, Wenze Prabath, Biju G Boerma, Marjan Wang, Junru Zhou, Daohong Hauer-Jensen, Martin |
| description | Bone marrow transplantation (BMT) substantially improves 10-day survival after total body irradiation (TBI), consistent with an effect on intestinal radiation death. Total body irradiation, in addition to injuring the intestinal epithelium, also perturbs the mucosal immune system, the largest immune system in the body. This study focused on how transplanted bone marrow cells (BMCs) help restore mucosal immune cell populations after sublethal TBI (8.0 Gy). We further evaluated whether transplanted BMCs: (a) home to sites of radiation injury using green fluorescent protein labeled bone marrow; and (b) contribute to restoring the mucosal barrier in vivo. As expected, BMT accelerated recovery of peripheral blood (PB) cells. In the intestine, BMT was associated with significant early recovery of mucosal granulocytes (P = 0.005). Bone marrow transplantation did not affect mucosal macrophages or lymphocyte populations at early time points, but enhanced the recovery of these cells from day 14 onward (P = 0.03). Bone marrow transplantation also attenuated radiation-induced increase of intestinal CXCL1 and restored IL-10 levels (P = 0.001). Most importantly, BMT inhibited the post-radiation increase in intestinal permeability after 10 Gy TBI (P = 0.02) and modulated the expression of tight junction proteins (P = 0.01–0.05). Green fluorescent protein-positive leukocytes were observed both in intestinal tissue and in PB. These findings strongly suggest that BMT, in addition to enhancing general hematopoietic and immune system recovery, helps restore the intestinal immune system and enhances intestinal mucosal barrier function. These findings may be important in the development and understanding of strategies to alleviate or treat intestinal radiation toxicity. |
| doi_str_mv | 10.1667/RR13548.1 |
| format | Article |
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Total body irradiation, in addition to injuring the intestinal epithelium, also perturbs the mucosal immune system, the largest immune system in the body. This study focused on how transplanted bone marrow cells (BMCs) help restore mucosal immune cell populations after sublethal TBI (8.0 Gy). We further evaluated whether transplanted BMCs: (a) home to sites of radiation injury using green fluorescent protein labeled bone marrow; and (b) contribute to restoring the mucosal barrier in vivo. As expected, BMT accelerated recovery of peripheral blood (PB) cells. In the intestine, BMT was associated with significant early recovery of mucosal granulocytes (P = 0.005). Bone marrow transplantation did not affect mucosal macrophages or lymphocyte populations at early time points, but enhanced the recovery of these cells from day 14 onward (P = 0.03). Bone marrow transplantation also attenuated radiation-induced increase of intestinal CXCL1 and restored IL-10 levels (P = 0.001). Most importantly, BMT inhibited the post-radiation increase in intestinal permeability after 10 Gy TBI (P = 0.02) and modulated the expression of tight junction proteins (P = 0.01–0.05). Green fluorescent protein-positive leukocytes were observed both in intestinal tissue and in PB. These findings strongly suggest that BMT, in addition to enhancing general hematopoietic and immune system recovery, helps restore the intestinal immune system and enhances intestinal mucosal barrier function. These findings may be important in the development and understanding of strategies to alleviate or treat intestinal radiation toxicity.</description><identifier>ISSN: 0033-7587</identifier><identifier>EISSN: 1938-5404</identifier><identifier>DOI: 10.1667/RR13548.1</identifier><identifier>PMID: 24568131</identifier><language>eng</language><publisher>United States: The Radiation Research Society</publisher><subject>Animals ; Blood ; Blood Cell Count ; Bone marrow ; Bone Marrow Transplantation ; Chemokines - metabolism ; Epithelial cells ; Immune system ; Interleukin-10 - biosynthesis ; Interleukin-12 - metabolism ; Intestinal Mucosa - immunology ; Intestinal Mucosa - metabolism ; Intestinal Mucosa - pathology ; Intestinal Mucosa - radiation effects ; Intestines ; Irradiation ; Jejunum ; Jejunum - immunology ; Jejunum - radiation effects ; Lymphocytes ; Male ; Mice ; Permeability - radiation effects ; Physical trauma ; Radiation injuries ; Radiation Injuries - blood ; Radiation Injuries - immunology ; Radiation Injuries - metabolism ; Radiation Injuries - surgery ; REGULAR ARTICLES ; Tight Junctions - metabolism ; Tight Junctions - radiation effects ; Transplantation ; Traumatic brain injury ; Whole-Body Irradiation - adverse effects</subject><ispartof>Radiation research, 2014-03, Vol.181 (3), p.229-239</ispartof><rights>Copyright © 2014 Radiation Research Society</rights><rights>Copyright Allen Press Publishing Services Mar 2014</rights><rights>2014 by Radiation Research Society. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b457t-99e190ee937476ad32a8ca9db382bed104ea3d54ac6b344c728dda0280c97f933</citedby><cites>FETCH-LOGICAL-b457t-99e190ee937476ad32a8ca9db382bed104ea3d54ac6b344c728dda0280c97f933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24545123$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24545123$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,27923,27924,58016,58249</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24568131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Garg, Sarita</creatorcontrib><creatorcontrib>Wang, Wenze</creatorcontrib><creatorcontrib>Prabath, Biju G</creatorcontrib><creatorcontrib>Boerma, Marjan</creatorcontrib><creatorcontrib>Wang, Junru</creatorcontrib><creatorcontrib>Zhou, Daohong</creatorcontrib><creatorcontrib>Hauer-Jensen, Martin</creatorcontrib><title>Bone Marrow Transplantation Helps Restore the Intestinal Mucosal Barrier after Total Body Irradiation in Mice</title><title>Radiation research</title><addtitle>Radiat Res</addtitle><description>Bone marrow transplantation (BMT) substantially improves 10-day survival after total body irradiation (TBI), consistent with an effect on intestinal radiation death. Total body irradiation, in addition to injuring the intestinal epithelium, also perturbs the mucosal immune system, the largest immune system in the body. This study focused on how transplanted bone marrow cells (BMCs) help restore mucosal immune cell populations after sublethal TBI (8.0 Gy). We further evaluated whether transplanted BMCs: (a) home to sites of radiation injury using green fluorescent protein labeled bone marrow; and (b) contribute to restoring the mucosal barrier in vivo. As expected, BMT accelerated recovery of peripheral blood (PB) cells. In the intestine, BMT was associated with significant early recovery of mucosal granulocytes (P = 0.005). Bone marrow transplantation did not affect mucosal macrophages or lymphocyte populations at early time points, but enhanced the recovery of these cells from day 14 onward (P = 0.03). Bone marrow transplantation also attenuated radiation-induced increase of intestinal CXCL1 and restored IL-10 levels (P = 0.001). Most importantly, BMT inhibited the post-radiation increase in intestinal permeability after 10 Gy TBI (P = 0.02) and modulated the expression of tight junction proteins (P = 0.01–0.05). Green fluorescent protein-positive leukocytes were observed both in intestinal tissue and in PB. These findings strongly suggest that BMT, in addition to enhancing general hematopoietic and immune system recovery, helps restore the intestinal immune system and enhances intestinal mucosal barrier function. These findings may be important in the development and understanding of strategies to alleviate or treat intestinal radiation toxicity.</description><subject>Animals</subject><subject>Blood</subject><subject>Blood Cell Count</subject><subject>Bone marrow</subject><subject>Bone Marrow Transplantation</subject><subject>Chemokines - metabolism</subject><subject>Epithelial cells</subject><subject>Immune system</subject><subject>Interleukin-10 - biosynthesis</subject><subject>Interleukin-12 - metabolism</subject><subject>Intestinal Mucosa - immunology</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestinal Mucosa - pathology</subject><subject>Intestinal Mucosa - radiation effects</subject><subject>Intestines</subject><subject>Irradiation</subject><subject>Jejunum</subject><subject>Jejunum - immunology</subject><subject>Jejunum - radiation effects</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Mice</subject><subject>Permeability - radiation effects</subject><subject>Physical trauma</subject><subject>Radiation injuries</subject><subject>Radiation Injuries - blood</subject><subject>Radiation Injuries - immunology</subject><subject>Radiation Injuries - metabolism</subject><subject>Radiation Injuries - surgery</subject><subject>REGULAR ARTICLES</subject><subject>Tight Junctions - metabolism</subject><subject>Tight Junctions - radiation effects</subject><subject>Transplantation</subject><subject>Traumatic brain injury</subject><subject>Whole-Body Irradiation - adverse 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Res</addtitle><date>2014-03-01</date><risdate>2014</risdate><volume>181</volume><issue>3</issue><spage>229</spage><epage>239</epage><pages>229-239</pages><issn>0033-7587</issn><eissn>1938-5404</eissn><abstract>Bone marrow transplantation (BMT) substantially improves 10-day survival after total body irradiation (TBI), consistent with an effect on intestinal radiation death. Total body irradiation, in addition to injuring the intestinal epithelium, also perturbs the mucosal immune system, the largest immune system in the body. This study focused on how transplanted bone marrow cells (BMCs) help restore mucosal immune cell populations after sublethal TBI (8.0 Gy). We further evaluated whether transplanted BMCs: (a) home to sites of radiation injury using green fluorescent protein labeled bone marrow; and (b) contribute to restoring the mucosal barrier in vivo. As expected, BMT accelerated recovery of peripheral blood (PB) cells. In the intestine, BMT was associated with significant early recovery of mucosal granulocytes (P = 0.005). Bone marrow transplantation did not affect mucosal macrophages or lymphocyte populations at early time points, but enhanced the recovery of these cells from day 14 onward (P = 0.03). Bone marrow transplantation also attenuated radiation-induced increase of intestinal CXCL1 and restored IL-10 levels (P = 0.001). Most importantly, BMT inhibited the post-radiation increase in intestinal permeability after 10 Gy TBI (P = 0.02) and modulated the expression of tight junction proteins (P = 0.01–0.05). Green fluorescent protein-positive leukocytes were observed both in intestinal tissue and in PB. These findings strongly suggest that BMT, in addition to enhancing general hematopoietic and immune system recovery, helps restore the intestinal immune system and enhances intestinal mucosal barrier function. These findings may be important in the development and understanding of strategies to alleviate or treat intestinal radiation toxicity.</abstract><cop>United States</cop><pub>The Radiation Research Society</pub><pmid>24568131</pmid><doi>10.1667/RR13548.1</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Radiation research, 2014-03, Vol.181 (3), p.229-239 |
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| subjects | Animals Blood Blood Cell Count Bone marrow Bone Marrow Transplantation Chemokines - metabolism Epithelial cells Immune system Interleukin-10 - biosynthesis Interleukin-12 - metabolism Intestinal Mucosa - immunology Intestinal Mucosa - metabolism Intestinal Mucosa - pathology Intestinal Mucosa - radiation effects Intestines Irradiation Jejunum Jejunum - immunology Jejunum - radiation effects Lymphocytes Male Mice Permeability - radiation effects Physical trauma Radiation injuries Radiation Injuries - blood Radiation Injuries - immunology Radiation Injuries - metabolism Radiation Injuries - surgery REGULAR ARTICLES Tight Junctions - metabolism Tight Junctions - radiation effects Transplantation Traumatic brain injury Whole-Body Irradiation - adverse effects |
| title | Bone Marrow Transplantation Helps Restore the Intestinal Mucosal Barrier after Total Body Irradiation in Mice |
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