BACKGROUND: Prophylactic ganciclovir (GCV) is used in high-risk renal transplant patients to prevent acute cytomegalovirus (CMV) disease, but its impact on inflammation within the allograft itself remains undefined. METHODS: To study the effect of GCV prophylaxis on allograft inflammation, murine CMV (MCMV)-infected allografts were analyzed in a murine donor positive/recipient negative allogeneic renal transplantation model by flow cytometry and immunofluorescent staining. RESULTS: By flow cytometry, CD45+ leukocyte infiltrates were more abundant in MCMV-infected allografts at 14 days posttransplant compared with uninfected grafts (P<0.01) and decreased in the presence of GCV (P<0.05). CD11c+ dendritic cells, Gr-1+ myeloid cells, CD204+ macrophages, and CD49b+ natural killer cells were reduced in GCV-treated allografts compared with MCMV-infected grafts without GCV treatment (P<0.05). However, GCV failed to reduce these cell types to levels found in MCMV-uninfected allografts. By day 7 after cessation of GCV prophylaxis, dendritic cells, macrophages, and natural killer cells increased in number and became statistically indistinguishable from numbers of cells found in MCMV-infected allografts without GCV. GCV treatment did not affect the numbers of CD4+, CD8+, or CD19+/B220+ lymphocytes infiltrating the allografts. Infiltrates were confirmed histologically by immunofluorescent staining for CD3+ and CD11b+ cells. CONCLUSIONS: In this model, MCMV-infected allografts developed significantly greater innate and adaptive leukocytic infiltrates compared with uninfected grafts. GCV attenuated the MCMV-associated innate leukocyte infiltrates in infected allografts but not the lymphocytic infiltrates. The attenuated innate response was limited to the period of GCV prophylaxis.
BACKGROUND: Prophylactic ganciclovir (GCV) is used in high-risk renal transplant patients to prevent acute cytomegalovirus (CMV) disease, but its impact on inflammation within the allograft itself remains undefined. METHODS: To study the effect of GCV prophylaxis on allograft inflammation, murine CMV (MCMV)-infected allografts were analyzed in a murinedonor positive/recipient negative allogeneic renal transplantation model by flow cytometry and immunofluorescent staining. RESULTS: By flow cytometry, CD45+ leukocyte infiltrates were more abundant in MCMV-infected allografts at 14 days posttransplant compared with uninfected grafts (P<0.01) and decreased in the presence of GCV (P<0.05). CD11c+ dendritic cells, Gr-1+ myeloid cells, CD204+ macrophages, and CD49b+ natural killer cells were reduced in GCV-treated allografts compared with MCMV-infected grafts without GCV treatment (P<0.05). However, GCV failed to reduce these cell types to levels found in MCMV-uninfected allografts. By day 7 after cessation of GCV prophylaxis, dendritic cells, macrophages, and natural killer cells increased in number and became statistically indistinguishable from numbers of cells found in MCMV-infected allografts without GCV. GCV treatment did not affect the numbers of CD4+, CD8+, or CD19+/B220+ lymphocytes infiltrating the allografts. Infiltrates were confirmed histologically by immunofluorescent staining for CD3+ and CD11b+ cells. CONCLUSIONS: In this model, MCMV-infected allografts developed significantly greater innate and adaptive leukocytic infiltrates compared with uninfected grafts. GCV attenuated the MCMV-associated innate leukocyte infiltrates in infected allografts but not the lymphocytic infiltrates. The attenuated innate response was limited to the period of GCV prophylaxis.
Authors: B Sis; M Mengel; M Haas; R B Colvin; P F Halloran; L C Racusen; K Solez; W M Baldwin; E R Bracamonte; V Broecker; F Cosio; A J Demetris; C Drachenberg; G Einecke; J Gloor; D Glotz; E Kraus; C Legendre; H Liapis; R B Mannon; B J Nankivell; V Nickeleit; J C Papadimitriou; P Randhawa; H Regele; K Renaudin; E R Rodriguez; D Seron; S Seshan; M Suthanthiran; B A Wasowska; A Zachary; A Zeevi Journal: Am J Transplant Date: 2010-01-29 Impact factor: 8.086
Authors: Lorraine C Racusen; Robert B Colvin; Kim Solez; Michael J Mihatsch; Philip F Halloran; Patricia M Campbell; Michael J Cecka; Jean-Pierre Cosyns; Anthony J Demetris; Michael C Fishbein; Agnes Fogo; Peter Furness; Ian W Gibson; Denis Glotz; Pekka Hayry; Lawrence Hunsickern; Michael Kashgarian; Ronald Kerman; Alex J Magil; Robert Montgomery; Kunio Morozumi; Volker Nickeleit; Parmjeet Randhawa; Heinz Regele; Daniel Seron; Surya Seshan; Stale Sund; Kiril Trpkov Journal: Am J Transplant Date: 2003-06 Impact factor: 8.086
Authors: Mao Li; Srinivasa Rao Boddeda; Bo Chen; Qiang Zeng; Trenton R Schoeb; Victoria M Velazquez; Masako Shimamura Journal: Am J Transplant Date: 2018-05-07 Impact factor: 8.086
Authors: Masako Shimamura; Maria C Seleme; Lingling Guo; Ute Saunders; Trenton R Schoeb; James F George; William J Britt Journal: Transplantation Date: 2013-01-15 Impact factor: 4.939
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