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D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion.
- Source :
-
Blood . 12/1/2011, Vol. 118 Issue 23, p6220-6229. 10p. - Publication Year :
- 2011
-
Abstract
- Lymphatic endothelial cells are important for efficient flow of antigen-bearing fluid and antigen-presenting cells (APC5) from peripheral sites to lymph nodes (LN5). APC movement to LNs is dependent on the constitutive chemokine receptor CCR7, although how conflicting inflammatory and constitutive chemokine cues are integrated at lymphatic surfaces during this process is not understood. Here we reveal a previously unrecognized aspect of the regulation of this process. The D6 chemokine-scavenging receptor, which is expressed on lymphatic endothelial cells (LEC5), maintains lymphatic surfaces free of inflammatory CC-chemokines and minimizes interaction of inflammatory leukocytes with these surfaces. D6 does not alter the level of CCR7 ligands on LEC5, thus ensuring selective presentation of homeostatic chemokines for interaction with CCR7+APC5. Accordingly, in D6deficient mice, inflammatory CC chemokine adherence to LEC5 results in inappropriate perilymphatic accumulation of inflammatory leukocytes at peripheral inflamed sites and draining LNs. This results in lymphatic congestion and impaired movement of APC5, and fluid, from inflamed sites to LNs. We propose that D6, by suppressing inflammatory chemokine binding to lymphatic surfaces, and thereby preventing inappropriate inflammatory leukocyte adherence, is a key regulator of lymphatic function and a novel, and indispensable, contributor to the integration of innate and adaptive immune responses. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CELL migration
*LYMPH nodes
*CHEMOKINES
*LEUCOCYTES
*NATURAL immunity
Subjects
Details
- Language :
- English
- ISSN :
- 00064971
- Volume :
- 118
- Issue :
- 23
- Database :
- Academic Search Index
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 69961483
- Full Text :
- https://doi.org/10.1182/blood-2011-03-344044