Normal Human Kidney HLA-DR–Expressing Renal Microvascular Endothelial Cells
Autor: | Susan K. Anderson, David M. Coder, Kimberly A. Muczynski, David M. Ekle |
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Rok vydání: | 2003 |
Předmět: |
Umbilical Veins
Transcription Genetic T cell Population Gene Expression Antineoplastic Agents Cell Separation Human leukocyte antigen In Vitro Techniques Kidney Major histocompatibility complex Interferon-gamma Jurkat Cells MHC class I HLA-DR CIITA medicine Humans Promoter Regions Genetic education Lung MHC class II education.field_of_study biology HLA-DR Antigens General Medicine Flow Cytometry Molecular biology Platelet Endothelial Cell Adhesion Molecule-1 Phenotype medicine.anatomical_structure Nephrology Immunology biology.protein Endothelium Vascular Biomarkers |
Zdroj: | Journal of the American Society of Nephrology. 14:1336-1348 |
ISSN: | 1046-6673 |
DOI: | 10.1097/01.asn.0000061778.08085.9f |
Popis: | Human, but not murine, renal peritubular and glomerular capillaries constitutively express class II major histocompatibility (MHC) proteins at high levels in normal human kidney. Expression of class II proteins on renal microvascular endothelial cells (RMEC) makes it available to circulating lymphocytes and imparts a surveillance capacity to RMEC for controlling inflammatory responses. In this report, the co-expression of HLA-DR and the endothelial marker CD31 are used to identify RMEC as a distinct population of cells within a standard renal biopsy using flow cytometry. A three-laser, multicolor flow cytometry analysis using Alexa dyes, developed for characterizing the expression of cell surface antigens, identifies RMEC as a population separate from HLA-DR-expressing leukocytes. HLA-DR RMEC co-express HLA-DP and HLA-DQ. RMEC also express the T cell costimulatory factor CD58 but not CD80, CD86, or CD40. On the basis of high HLA-DR expression, RMEC are isolated for culture using fluorescence-activated cell sorting and magnetic beads. Cultured RMEC require normal basal physiologic concentrations of gamma interferon (gammaIFN) to maintain HLA protein expression. This expression is regulated by CIITA, the MHC class II-specific transcription factor. Four tissue-specific promoters have been described for CIITA. In freshly isolated RMEC, RT-PCR and hybridization using specific oligonucleotide probes to CIITA promoter sequences identify only the statin-sensitive gammaIFN-induced promoter IV of CIITA. Therefore, the constitutive expression of HLA-DR on RMEC in normal human kidney is located in a position for immune surveillance, depends on basal physiologic concentrations of gammaIFN, and may be amenable to regulation with statins. |
Databáze: | OpenAIRE |
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