PMID- 22222784 OWN - NLM STAT- MEDLINE DCOM- 20120420 LR - 20220331 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 93 IP - 4 DP - 2012 Feb 27 TI - Comparative study on signal transduction in endothelial cells after anti-a/b and human leukocyte antigen antibody reaction: implication of accommodation. PG - 390-7 LID - 10.1097/TP.0b013e3182424df3 [doi] AB - BACKGROUND: Recent development of immunosuppressive therapy has provided a platform for clinical human leukocyte antigen (HLA)- and ABO-incompatible kidney transplantation. However, the prognosis seems to be different between the two. Accommodation, the condition of no injury even in the presence of antidonor antibody, is one of the key factors for successful transplantation with antidonor antibody. The purpose of this study was to compare signal transduction between anti-A/B and anti-HLA antibody reaction and to elucidate the mechanisms underlying accommodation. METHODS: Blood type A- or B-transferase gene was transfected into human EA.hy926 endothelial cells. After cell sorting, A- or B-expressing cells at high levels were obtained. The effects of anti-HLA and anti-A/B antibody binding on complement-mediated cytotoxicity and signal transduction were examined. RESULTS: Preincubation with anti-HLA antibodies only at low levels (<10% of saturation level) or anti-A/B antibodies at high levels (even at near saturation levels) for 24 hr resulted in resistance to complement-mediated cytotoxicity. Anti-A/B antibody ligation inactivated ERK1/2 pathway and increased complement regulatory proteins such as CD55 and CD59, whereas anti-HLA ligation activated PI3K/AKT pathway and increased cytoprotective genes such as hemeoxygenase-1 and ferritin H. CONCLUSION: Complement inhibition by upregulation of CD55 and CD59 through ERK1/2 inactivation might play a substantial role in accommodation after ABO-incompatible transplantation, which could also explain the intriguing finding of C4d deposition in the graft without rejection. FAU - Iwasaki, Kenta AU - Iwasaki K AD - Department of Applied Immunology, Nagoya University School of Medicine, Nagoya, Japan. FAU - Miwa, Yuko AU - Miwa Y FAU - Ogawa, Haruko AU - Ogawa H FAU - Yazaki, Satoko AU - Yazaki S FAU - Iwamoto, Masaki AU - Iwamoto M FAU - Furusawa, Tadashi AU - Furusawa T FAU - Onishi, Akira AU - Onishi A FAU - Kuzuya, Takafumi AU - Kuzuya T FAU - Haneda, Masataka AU - Haneda M FAU - Watarai, Yoshihiko AU - Watarai Y FAU - Uchida, Kazuharu AU - Uchida K FAU - Kobayashi, Takaaki AU - Kobayashi T LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (ABO Blood-Group System) RN - 0 (Antibodies, Anti-Idiotypic) RN - 0 (CD55 Antigens) RN - 0 (CD59 Antigens) RN - 0 (HLA Antigens) RN - 9007-36-7 (Complement System Proteins) RN - 9013-31-4 (Apoferritins) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Oncogene Protein v-akt) SB - IM CIN - Transplantation. 2012 Feb 27;93(4):354-5. PMID: 22277981 MH - ABO Blood-Group System/*immunology MH - Antibodies, Anti-Idiotypic/*immunology/pharmacology MH - Apoferritins/physiology MH - CD55 Antigens/physiology MH - CD59 Antigens/physiology MH - Cells, Cultured MH - Complement System Proteins/physiology MH - Endothelial Cells/drug effects/immunology/*physiology MH - Graft Rejection/immunology/*prevention & control MH - HLA Antigens/*immunology MH - Heme Oxygenase-1/physiology MH - Humans MH - MAP Kinase Signaling System/physiology MH - Oncogene Protein v-akt/physiology MH - Organ Transplantation/*physiology MH - Phosphatidylinositol 3-Kinases/physiology MH - Signal Transduction/immunology/*physiology EDAT- 2012/01/10 06:00 MHDA- 2012/04/21 06:00 CRDT- 2012/01/07 06:00 PHST- 2012/01/07 06:00 [entrez] PHST- 2012/01/10 06:00 [pubmed] PHST- 2012/04/21 06:00 [medline] AID - 10.1097/TP.0b013e3182424df3 [doi] PST - ppublish SO - Transplantation. 2012 Feb 27;93(4):390-7. doi: 10.1097/TP.0b013e3182424df3.