Expression of human immunodeficiency virus (HIV)–binding lectin DC-SIGNR: Consequences for HIV infection and immunity

• Published in: Human pathology Vol. 33; no. 6; pp. 652 - 659
• Main Authors: Soilleux, Elizabeth J., Morris, Lesley S., Rushbrook, Simon, Lee, Benhur, Coleman, Nicholas
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2002; Elsevier
• Subjects: Animals; Biological and medical sciences; Biomarkers, Tumor; CD4 Antigens - biosynthesis; Cell Adhesion Molecules; Cell Differentiation; Cell Line; Chickens; DC-SIGN; DC-SIGNR; E-Selectin - analysis; endothelium; Endothelium - cytology; Endothelium - metabolism; Hemangioma - complications; Hemangioma - pathology; HIV Infections - immunology; HIV-1; HLA-DR Antigens - analysis; human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Lectins - biosynthesis; Lectins, C-Type; liver; Liver - cytology; Liver - metabolism; Lymph Nodes - pathology; Medical sciences; Phenotype; Rabbits; Receptors, CCR5 - biosynthesis; Receptors, Cell Surface - biosynthesis; Surface Properties; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; endothelium; BSA; HIV; TBS; liver; ALP; DC-SIGN; HRP; DC-SIGNR; human immunodeficiency virus; Human; Immunohistochemistry; Binding; Immunopathology; Lectin; Immune response; Lymph node; Pathogenesis; Retroviridae; Confocal microscopy; AIDS; Immune deficiency; Lentivirus; Immunity; Infection; Virus; Pathology; Viral disease; Human immunodeficiency virus; Immunofluorescence
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1053/hupa.2002.124036

DC-SIGNR is a human immunodeficiency virus (HIV)-binding C-type lectin that is expressed on endothelium in the hepatic sinusoids, lymph node sinuses and placenta. Like closely related DC-SIGN, DC-SIGNR can bind both ICAM-3 and HIV and can potentiate HIV infection of T lymphocytes in trans. In the present study we have investigated reasons underlying the restricted distribution of DC-SIGNR and have examined DC-SIGNR expression in relation to HIV entry receptors. We show that DC-SIGNR expression does not depend on endothelial cell specialization or on activation state. DC-SIGNR-positive endothelium continues to express DC-SIGNR in conditions of hyperplasia, whereas the molecule is lost after neoplastic transformation, most likely as a result of changes in the microenvironment of the endothelial cells. We have further shown that CCR5, but not CD4, is coexpressed with DC-SIGNR on hepatic sinusoidal and placental capillary endothelial cells. However, CD4-positive CCR5-positive cells, such as hepatic Kupffer cells, placental Hofbauer cells, and CD4-positive T lymphocytes in lymph nodes, can be found adjacent to DC-SIGNR–positive endothelium. Therefore, DC-SIGNR may be able to mediate HIV infection of these cells in trans. Finally, we demonstrate that DC-SIGN and DC-SIGNR can be coexpressed on lymph node sinus endothelial cells, which may lead to modulation of the function of both molecules. HUM PATHOL 33:652-659. Copyright 2002, Elsevier Science (USA). All rights reserved.