Regulated expression of the pathogen receptor dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin in THP-1 human leukemic cells, monocytes, and macrophages.
Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and mediates binding and internalization of pathogens such as virus (human immunodeficiency virus, hepatitis C), bacteria (Mycobacterium), fungi, and parasites. DC-SIGN expression in vivo is primarily restricted to interstitial dendritic cells (DC) and certain tissue macrophages. We now report that leukemic THP-1 cells, widely used as a model for monocyte-macrophage differentiation, express very low basal levels of DC-SIGN and that DC-SIGN expression in THP-1 cells is regulated during differentiation. Differentiation-inducing agents (phorbol ester, bryostatin) conveyed THP-1 cells with the ability to up-regulate DC-SIGN mRNA levels and cell surface expression in response to interleukin-4 (IL-4) or IL-13. DC-SIGN up-regulation required a functional JAK-STAT signaling pathway, was inhibited in the presence of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha), and conferred THP-1 cells with increased pathogen recognition and T cell stimulatory capabilities. The up-regulation of DC-SIGN on THP-1 cells resembles its inducible expression on monocytes and macrophages, where DC-SIGN expression is also induced by IL-4/IL-13 and negatively regulated by TNF-alpha, LPS, and vitamin D(3). These results point to THP-1 cells as a useful cellular system to characterize the pathogen-binding capabilities of DC-SIGN and to dissect the molecular mechanisms that control its regulated and tissue-specific expression in myeloid dendritic cells, and the results suggest that DC-SIGN constitutes a marker for both DC and alternatively activated macrophages.
Puig-Kröger
Amaya
A
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu, 9 28040 Madrid, Spain.
Serrano-Gómez
Diego
D
Caparrós
Esther
E
Domínguez-Soto
Angeles
A
Relloso
Miguel
M
Colmenares
María
M
Martínez-Muñoz
Laura
L
Longo
Natividad
N
Sánchez-Sánchez
Noelia
N
Rincon
Mercedes
M
Rivas
Luis
L
Sánchez-Mateos
Paloma
P
Fernández-Ruiz
Elena
E
Corbí
Angel L
AL
D015815:Cell Adhesion Molecules / Q000235:genetics*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000235:genetics*; D007938:Leukemia / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction; D015854:Up-Regulation; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015847:Interleukin-4; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin