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.
Original language | English |
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Article number | e85699 |
Journal | PLoS ONE |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 22 Jan 2014 |
Funding
Israel Science Foundation; U.S. Israel Binational Science Foundation (BSF), FAMRI; Flight Attendant Medical Research Institute Foundation; Minerva Foundation, Germany; European Research Council (ERC); FP7 ITN "Stroma''R. Alon is an incumbent of the Linda Jacobs Chair in Immune and Stem Cell Research, and his research is supported by the Israel Science Foundation, the U.S. Israel Binational Science Foundation (BSF), FAMRI, the Flight Attendant Medical Research Institute Foundation, and the Minerva Foundation, Germany. Michael Sixt's research is supported by the European Research Council (ERC Starting grant) and by the FP7 ITN "Stroma''. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
All Science Journal Classification (ASJC) codes
- General
- General Biochemistry,Genetics and Molecular Biology
- General Agricultural and Biological Sciences