Lymph-Borne Chemokines and Other Low Molecular Weight Molecules Reach High Endothelial Venules via Specialized Conduits While a Functional Barrier Limits Access to the Lymphocyte Microenvironments…

By J. E. Gretz, C. Norbury, Arthur O. Anderson, A. Proudfoot, S. Shaw. Journal of Experimental Medicine, 2000

614 citations recorded by the source corpus.

Lymph-borne, soluble factors (e.g., chemokines and others) influence lymphocyte recirculation and endothelial phenotype at high endothelial venules (HEVs) in lymph node cortex. Yet the route lymph-borne soluble molecules travel from the subcapsular sinus to the HEVs is unclear. Therefore, we injected subcutaneously into mice and rats a wide variety of fluorophore-labeled, soluble molecules and examined their distribution in the draining lymph nodes. Rather than percolating throughout the draining lymph node, all molecules, including microbial lipopolysaccharide, were very visible in the subcapsular and medullary sinuses but were largely excluded from the cortical lymphocyte microenvironments. Exclusion prevailed even during the acute lymph node enlargement accompanying viral infection. However, low molecular mass (MW) molecules, including chemokines, did gain entry into the cortex, but in a very defined manner. Low MW, fluorophore-labeled molecules highlighted the subcapsular sinus, the reticular fibers, and the abluminal and luminal surfaces of the associated HEVs. These low MW molecules were in the fibers of the reticular network, a meshwork of collagen fibers ensheathed by fibroblastic reticular cells that connects the subcapsular sinus floor and the HEVs by intertwining with their basement membranes. Thus, low MW, lymph-borne molecules, including chemokines, traveled rapidly from the subcapsular sinus to the HEVs using the reticular network as a conduit.

Subfields: Immunology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/163cf620e21c7d6806797f9c6690cc431af4b2d5

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In Immunology

1. J. Cyster
2. A. Luster
3. F. Batista
4. Naomi E. Harwood
5. Ulrich H. von Andrian
6. T. Okada
7. R. Mebius
8. S. Luther

In Immunology and Allergy

1. F. Batista
2. Naomi E. Harwood
3. J. Cyster
4. M. Aurrand-Lions
5. B. Imhof
6. B. Hinz
7. H. Wiig
8. M. Swartz

Citations in the corpus

• Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. (2005, background): “…days) time points after picutaneous application of TRITC (Figure 4 and data ot shown) suggest that the labeled DCs have acquired RITC in the skin (Gretz et al., 2000; Itano et al., 2003). n support of that view, TRITC was absent at all timeoints from nonskin-derived DC subsets found in LNs,…”
• Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells (2007, background): “Studies have indicated that immune complexes do not travel freely into the parenchyma of lymphoid tissue”
• Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells (2007, background): “Such conduits drain fluid and small molecules from the subcapsular sinus to high endothelial venules (HEVs”
• Structure and function of the spleen (2005, background): “In a further comparison between the lymph nodes and the splenic white pulp, the presence of a tubular network has been reported for both lymphoid organ”
• Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. (2012, background): “Lymph is also directed from the sinus into the cortex by narrow conduits (200 nm to 3 m), lined by fibroblastic reticular cells, that regulate the flow of unopsonized small molecules ( 70 kDa) to the T-cell zone (159, 253, 392, 393).”
• Follicular shuttling of marginal zone B cells facilitates antigen transport (2008, background): “Like lymph nodes, the white pulp cords of spleen are surrounded by stromal cells and associated extracellular matrix that together form a barrier restricting the free diffusion of molecules that are the size of antibodie”
• Adhesion mechanisms regulating the migration of monocytes (2004, background): “Chemokines (such as CCL3 and CXCL8) can be transported to the draining lymph nodes, where they are trapped on HEVs, subcapsular sinuses and reticular fibre”
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• Orchestrating the orchestrators: chemokines in control of T cell traffic (2008, background): “The lymph node conduit system, which communicates with the HEV perivenular space”
• Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells (2005, background): “Interfollicular regions are also rich in high endothelial venules, and other studies have indicated that DCs newly arriving in lymph nodes are often found near follicles or clustered around high endothelial venules [14,17,54], and small, soluble antigens can reach these regions via conduits that con”
• Homing and cellular traffic in lymph nodes (2003, background): “Lymph-borne molecules do not have free access to the lymphocyte compartmen”