PMID- 14510696 OWN - NLM STAT- MEDLINE DCOM- 20031212 LR - 20230124 IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 3 IP - 10 DP - 2003 Oct TI - Adenovirus transduction induces expression of multiple chemokines and chemokine receptors in murine beta cells and pancreatic islets. PG - 1230-41 AB - Adenoviral vectors are highly efficient for transferring genes to islets. However, the inflammatory and immune responses stimulated by adenovirus may be detrimental to islet survival. Given the role of chemokines and their receptors in inflammation, we analyzed their expression in isolated murine islets, in a murine beta cell line and in syngeneic islet grafts after adenovirus transduction (AdRSVLacZ). AdRSVLacZ transduction enhanced and induced the expression of a variety of chemokines. Transduced syngeneic transplanted islets showed significantly enhanced expression of multiple chemokines and receptors, including monocyte chemoattractant protein-1 (MCP-1), CC chemokine receptor 2 (CCR2) and regulated upon activation, normal T cell expressed and secreted (RANTES), compared with untransduced islet grafts. AdRSVLacZ-transduced islet grafts had significant mononuclear infiltrates, and in situ hybridization demonstrated intragraft expression of MCP-1, CCR2 and RANTES. Although adenovirus transduction did not impair in vitro insulin secretion, diabetes was reversed in only one of six recipients of a marginal mass of AdRSVLacZ-transduced islets, compared with six of six control recipients. In conclusion, multiple chemokines and chemokine receptors are expressed by murine islets constitutively and in response to adenovirus transduction. Adenovirus transduction impairs engraftment of marginal mass of transplanted islets. This is not because of direct vector toxicity of islet secretory capacity, but may be related to host innate immunity in response to adenovirus vector. FAU - Zhang, Nan AU - Zhang N AD - Recanati-Miller Transplantation Institute, Carl C Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY, USA. FAU - Schroppel, Bernd AU - Schroppel B FAU - Chen, Dongmei AU - Chen D FAU - Fu, Shuang AU - Fu S FAU - Hudkins, Kelly L AU - Hudkins KL FAU - Zhang, Haojiang AU - Zhang H FAU - Murphy, Barbara M AU - Murphy BM FAU - Sung, Randall S AU - Sung RS FAU - Bromberg, Jonathan S AU - Bromberg JS LA - eng GR - AI42840/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Chemokines) RN - 0 (DNA, Complementary) RN - 0 (Insulin) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 63231-63-0 (RNA) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adenoviridae/*genetics MH - Animals MH - Chemokine CCL2/biosynthesis MH - Chemokine CCL5/biosynthesis MH - Chemokines/*biosynthesis/genetics/metabolism MH - DNA, Complementary/metabolism MH - Gene Transfer Techniques MH - Genetic Vectors MH - Glucose/metabolism MH - In Situ Hybridization MH - Insulin/metabolism MH - Insulin Secretion MH - Islets of Langerhans/*metabolism MH - Islets of Langerhans Transplantation/methods MH - Mice MH - Mice, Inbred C57BL MH - Oligonucleotide Array Sequence Analysis MH - RNA/metabolism MH - Receptors, CCR2 MH - Receptors, Chemokine/*biosynthesis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Time Factors EDAT- 2003/09/27 05:00 MHDA- 2003/12/13 05:00 CRDT- 2003/09/27 05:00 PHST- 2003/09/27 05:00 [pubmed] PHST- 2003/12/13 05:00 [medline] PHST- 2003/09/27 05:00 [entrez] AID - S1600-6135(22)07635-3 [pii] AID - 10.1046/j.1600-6143.2003.00215.x [doi] PST - ppublish SO - Am J Transplant. 2003 Oct;3(10):1230-41. doi: 10.1046/j.1600-6143.2003.00215.x.