PMID- 17179229 OWN - NLM STAT- MEDLINE DCOM- 20070531 LR - 20231213 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 109 IP - 7 DP - 2007 Apr 1 TI - Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation. PG - 2806-14 AB - Human leukocyte antigen (HLA)-E belongs, with HLA-G and HLA-F, to the non-classic major histocompatibility complex (MHC) class I (Ib) molecules, broadly defined by a limited polymorphism and a restricted pattern of cellular expression. In contrast to HLA-G, the expression and function of HLA-E and HLA-F in physiologic and pathologic processes remain poorly established. In the present study, we show that HLA-E protein expression in normal human nonlymphoid organs is mainly restricted to endothelial cells (ECs). HLA-E is also basally expressed by B and T lymphocytes, natural killer (NK) cells and by macrophages. We demonstrate that tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and interferon gamma (IFNgamma) up-regulate the cell-surface expression of HLA-E on ECs in vitro and induce the release of soluble HLA-E (sHLA-E). HLA-E up-regulation protects IFN-gamma-activated ECs from NK-mediated cell lysis, while sHLA-E protects bystander cells. Finally, sHLA-E is not detected in normal sera, and increased serum levels correlate with disease activity in patients with antineutrophil cytoplasmic antibody-associated systemic vasculitis. Thus, HLA-E expression and release of sHLA-E are features of EC activation and emphasize immunoregulatory functions of the endothelium. The present identification of soluble HLA-E molecules may have important implications in understanding the pathogenesis of immune-mediated vascular diseases and for the diagnosis and monitoring of patients. FAU - Coupel, Stephanie AU - Coupel S AD - Institut National de la Sante et de la Recherche Medicale, Unit 643, Institut de Transplantation et de Recherche en Transplantation, Nantes, France. FAU - Moreau, Anne AU - Moreau A FAU - Hamidou, Mohamed AU - Hamidou M FAU - Horejsi, Vaclav AU - Horejsi V FAU - Soulillou, Jean-Paul AU - Soulillou JP FAU - Charreau, Beatrice AU - Charreau B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Cytokines) RN - 0 (DNA Primers) RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (KLRD1 protein, human) RN - 0 (NK Cell Lectin-Like Receptor Subfamily D) RN - 0 (Receptors, Immunologic) RN - 0 (Receptors, Natural Killer Cell) SB - IM MH - Base Sequence MH - Cells, Cultured MH - Cytokines/pharmacology MH - Cytotoxicity, Immunologic MH - DNA Primers/genetics MH - Endothelial Cells/drug effects/*immunology MH - Female MH - Gene Expression MH - HLA Antigens/blood/genetics/*metabolism MH - Histocompatibility Antigens Class I/blood/genetics/*metabolism MH - Humans MH - In Vitro Techniques MH - Killer Cells, Natural/immunology MH - Leukocytes/immunology MH - NK Cell Lectin-Like Receptor Subfamily D/metabolism MH - Pregnancy MH - Receptors, Immunologic/metabolism MH - Receptors, Natural Killer Cell MH - Solubility MH - Vasculitis/immunology MH - HLA-E Antigens EDAT- 2006/12/21 09:00 MHDA- 2007/06/01 09:00 CRDT- 2006/12/21 09:00 PHST- 2006/12/21 09:00 [pubmed] PHST- 2007/06/01 09:00 [medline] PHST- 2006/12/21 09:00 [entrez] AID - S0006-4971(20)41781-1 [pii] AID - 10.1182/blood-2006-06-030213 [doi] PST - ppublish SO - Blood. 2007 Apr 1;109(7):2806-14. doi: 10.1182/blood-2006-06-030213.