Background: Heparan sulfate (HS) is a glycosaminoglycan that is anchored to the outside of cell membranes. Under ordinary circumstances, it is not present in the interstitium, but under certain circumstances, mainly in the setting of inflammation and tissue repair, HS can be shed from the cell surface into the interstitium in a regulated fashion. Under these circumstances, interstitial HS seems to have an immunomodulatory function because of its binding of many cytokines. However, it is not known which cell types present at an inflammatory site are responsible for this shedding.
Objective: We have investigated the presence of interstitial HS by immunohistochemistry in various inflammatory skin diseases characterized by different compositions of the inflammatory infiltrate.
Results: Strong interstitial HS immunoreactivity was present only in diseases with a predominantly histiocytic infiltrate but not in diseases with a predominantly lymphocytic or neutrophilic infiltrate.
Conclusions: This indicates that histiocytes have a direct or indirect role in the HS shedding process. In the well-formed granulomas of sarcoidosis, interstitial HS immunoreactivity was spatially associated with the fibrotic ring at the periphery of the granulomas, but not with the center harboring the histiocytes. This suggests that histiocytes can stimulate fibroblasts to shed HS into the interstitium.
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http://dx.doi.org/10.1016/s0190-9622(03)00908-3 | DOI Listing |
Viruses
November 2024
Department of Ophthalmology and Visual Sciences, College of Medicine, University of Illinois Chicago, Chicago, IL 60612, USA.
The host enzyme heparanase (HPSE) facilitates the release of herpes simplex virus type 2 (HSV-2) from target cells by cleaving the viral attachment receptor heparan sulfate (HS) from infected cell surfaces. HPSE 2, an isoform of HPSE, binds to but does not possess the enzymatic activity needed to cleave cell surface HS. Our study demonstrates that HSV-2 infection significantly elevates HPSE 2 protein levels, impacting two distinct stages of viral replication.
View Article and Find Full Text PDFBMC Pulm Med
January 2025
Research Center of Occupational Medicine, Peking University Third Hospital, Beijing, 100191, China.
Elife
January 2025
Departments of Molecular & Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, United States.
Wnt/β-catenin signaling directs animal development and tissue renewal in a tightly controlled, cell- and tissue-specific manner. In the mammalian central nervous system, the atypical ligand Norrin controls angiogenesis and maintenance of the blood-brain barrier and blood-retina barrier through the Wnt/β-catenin pathway. Like Wnt, Norrin activates signaling by binding and heterodimerizing the receptors Frizzled (Fzd) and low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6), leading to membrane recruitment of the intracellular transducer Dishevelled (Dvl) and ultimately stabilizing the transcriptional coactivator β-catenin.
View Article and Find Full Text PDFBioorg Med Chem
December 2024
Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, via G. Colombo 81, 20133 Milano, Italy.
Sci Rep
December 2024
Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Waldeyerstrasse 15, D-48149, Münster, Germany.
The heparan sulfate (HS)-rich extracellular matrix (ECM) serves as an initial interaction site for the homotrimeric spike (S) protein of SARS-CoV-2 to facilitate subsequent docking to angiotensin-converting enzyme 2 (ACE2) receptors and cellular infection. More recent variants, notably Omicron, have evolved by swapping several amino acids to positively charged residues to enhance the interaction of the S-protein trimer with the negatively charged HS. However, these enhanced interactions may reduce Omicron's ability to move through the HS-rich ECM to effectively find ACE2 receptors and infect cells, raising the question of how to mechanistically explain HS-associated viral movement.
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