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Blood vessels pattern heparan sulfate gradients between their apical and basolateral aspects
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 1, p e85699 (2014)
- Publication Year :
- 2013
-
Abstract
- A hallmark of immune cell trafficking is directional guidance via gradients of soluble or surface bound chemokines. Vascular endothelial cells produce, transport and deposit either their own chemokines or chemokines produced by the underlying stroma. Endothelial heparan sulfate (HS) was suggested to be a critical scaffold for these chemokine pools, but it is unclear how steep chemokine gradients are sustained between the lumenal and ablumenal aspects of blood vessels. Addressing this question by semi-quantitative immunostaining of HS moieties around blood vessels with a pan anti-HS IgM mAb, we found a striking HS enrichment in the basal lamina of resting and inflamed post capillary skin venules, as well as in high endothelial venules (HEVs) of lymph nodes. Staining of skin vessels with a glycocalyx probe further suggested that their lumenal glycocalyx contains much lower HS density than their basolateral extracellular matrix (ECM). This polarized HS pattern was observed also in isolated resting and inflamed microvascular dermal cells. Notably, progressive skin inflammation resulted in massive ECM deposition and in further HS enrichment around skin post capillary venules and their associated pericytes. Inflammation-dependent HS enrichment was not compromised in mice deficient in the main HS degrading enzyme, heparanase. Our results suggest that the blood vasculature patterns steep gradients of HS scaffolds between their lumenal and basolateral endothelial aspects, and that inflammatory processes can further enrich the HS content nearby inflamed vessels. We propose that chemokine gradients between the lumenal and ablumenal sides of vessels could be favored by these sharp HS scaffold gradients.
- Subjects :
- Pathology
Chemokine
Anatomy and Physiology
Mouse
Immunofluorescence
lcsh:Medicine
Dermatitis
Basement Membrane
Extracellular matrix
chemistry.chemical_compound
Mice
Venules
Cricetinae
Molecular Cell Biology
lcsh:Science
Cells, Cultured
Glucuronidase
Skin
Cellular Stress Responses
Mice, Knockout
Multidisciplinary
Heparan sulfate
Animal Models
Cellular Structures
Cell biology
Extracellular Matrix
medicine.anatomical_structure
Basal lamina
Female
Chemokines
Cellular Types
Research Article
medicine.medical_specialty
Histology
Endothelium
Immune Cells
High endothelial venules
Immunology
Mice, Transgenic
CHO Cells
Biology
Glycocalyx
Cricetulus
Model Organisms
medicine
Animals
Humans
Heparanase
Inflammation
lcsh:R
Immunity
Endothelial Cells
Extracellular Matrix Composition
Capillaries
Mice, Inbred C57BL
chemistry
Microscopy, Fluorescence
biology.protein
Immunologic Techniques
570 Life sciences
biology
Blood Vessels
lcsh:Q
Endothelium, Vascular
Heparitin Sulfate
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....1cd6e6e0ed514f065f7b04abcb249f5f