Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunization using human papilloma virus (HPV)-L1 virus-like particles (VLPs) induces a robust and effective immune response, which has recently resulted in the implementation of the HPV-L1 VLP vaccination in health programs. However, during infection, HPV can escape immune surveillance leading to latency and disease. Dendritic cells (DCs) induce effective immune responses after vaccination, but might also induce immune modulation during infection. The interaction of HPV-L1 VLPs with mucosal DCs determines the immune response. However, little is known about the receptors on mucosal DC subsets involved in HPV-L1 VLP binding. Therefore, we set out to investigate the interaction of HPV-L1 VLPs with the different mucosal DC subsets; the subepithelial DCs and Langerhans cells (LCs). We observed strong binding of HPV-L1 VLPs to both DCs and LCs. We did not observe an involvement for C-type lectins such as dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) and langerin. The HPV-L1 VLP binding to DCs was mediated through heparan sulfates, since it was abrogated by heparinase-II treatment. The heparan sulfate proteoglycan syndecan-3 binds VLPs and is expressed on both DCs and LCs. Binding of VLPs to DCs, but not to LCs, strongly correlated with the levels of heparan sulfates and syndecan-3, suggesting that syndecan-3 is the main receptor for HPV-L1 VLPs on DCs. VLP interaction with DCs resulted in the up-regulation of co-stimulatory molecules and the production of the cytokines IL-6, IL-8, IL-10 and IL-12p40. Our results support an important role for syndecan-3 as a HPV receptor on DCs, which could be important for both vaccine development and understanding HPV pathogenesis.
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PMID:Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation. 1808 70

IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward DCs. IL-4 dose-dependently up-regulated the expression of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), CD80, CD206, and CD1a. Monocytes stained positive with Abs against heparan sulfate (HS) and chondroitin sulfate (CS) B (CSB; dermatan sulfate), but not with Abs that recognize CSA, CSC, and CSE. Inhibition of sulfation of monocyte/DC cell surface GAGs by sodium chlorate reduced the reactivity of sulfate-recognizing single-chain Abs. This correlated with hampered IL-4-induced DC differentiation as evidenced by lower expression of DC-SIGN and CD1a and a decreased DC-induced PBL proliferation, suggesting that sulfated monocyte cell surface GAGs support IL-4 activity. Furthermore, removal of cell surface chondroitin sulfates by chondroitinase ABC strongly impaired IL-4-induced STAT6 phosphorylation, whereas removal of HS by heparinase III had only a weak inhibitory effect. IL-4 bound to heparin and CSB, but not to HS, CSA, CSC, CSD, and CSE. Binding of IL-4 required iduronic acid, an N-sulfate group (heparin) and specific O sulfates (CSB and heparin). Together, these data demonstrate that monocyte cell surface chondroitin sulfates play an important role in the IL-4-driven differentiation of monocytes into DCs.
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PMID:Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells. 1832 73