Mannose Receptor Is a Novel Ligand for L-Selectin and Mediates Lymphocyte Binding to Lymphatic Endothelium

Irjala, Heikki; Johansson, Eva-Liz; Grénman, Reidar; Alanen, Kalle; Salmi, Marko; Jalkanen, Sirpa

doi:10.1084/jem.194.8.1033

Cited by 143 publications

(113 citation statements)

References 37 publications

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“…Binding assays were performed on frozen sections of murine lymph nodes as described [30]. Briefly, frozen sections were incubated with anti-Clever-1/Stabilin-1 Ab (1.26) or negative control Ab and thereafter, lymphocytes isolated from mesenteric lymph nodes were incubated on the sections for 15 min in static conditions, followed by 5 min of rotation at 60 rpm and then again for 15 min without rotation at 71C.…”

Section: In Vitro Binding Assaysmentioning

confidence: 99%

Clever‐1/Stabilin‐1 regulates lymphocyte migration within lymphatics and leukocyte entrance to sites of inflammation

et al. 2009

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Clever-1/Stabilin-1 is a scavenger receptor present on lymphatic and sinusoidal endothelium as well as on a subset of type II macrophages. It is also induced on vasculature at sites of inflammation. However, its in vivo function has remained practically unknown and this work addresses those unknown aspects. We demonstrate using in vivo models that Clever-1/Stabilin-1 mediates migration of T and B lymphocytes to the draining lymph nodes in vivo and identify the adhesive epitope of the Clever-1/Stabilin-1 molecule responsible for the interaction between lymphocytes and lymphatic endothelium. Moreover, we demonstrate that Ab blocking of Clever-1/Stabilin-1 efficiently inhibits peritonitis in mice by decreasing the entrance of granulocytes by 50%, while migration of monocytes and lymphocytes into the inflamed peritoneum is prevented almost completely. Despite efficient anti-inflammatory activity the Ab therapy does not dramatically dampen immune responses against the bacterial and foreign protein Ag tested and bacterial clearance. These results indicate that anti-Clever-1/Stabilin-1 treatment can target two different arms of the vasculature -traffic via lymphatics and inflamed blood vessels. IntroductionImmune cell trafficking between blood and lymphoid organs is an essential element in the proper functioning of the immune system. The mechanisms mediating lymphocyte entrance from the blood into the lymphoid organs and leukocyte trafficking to sites of inflammation are well known [1][2][3]. In contrast, mechanisms involved in lymphocyte migration from the periphery via the afferent lymphatics into the draining lymph nodes and their exit from the lymph nodes are poorly known. Besides lymphocytes, many tumors also use lymphatics for dissemination to distant sites of the body [4]. Eur. J. Immunol. 2009. 39: 3477-3487 DOI 10.1002 Innate immunity 3477Clever-1/Stabilin-1, also known as Feel-1, is a multifunctional molecule possessing scavenging ability on a subset of type II macrophages [5,6]. It is also present both on afferent and efferent lymphatic endothelial cells and sinusoidal endothelial cells in the liver and spleen [7][8][9][10]. In man, it is brightly expressed on high endothelial venules (HEV), which are the specific vessels within organized lymphatic tissues mediating lymphocyte entrance into the tissues, and on sinusoidal macrophages. Moreover, at sites of inflammation its expression is induced in flat-walled vessels. On lymphatic vasculature it is able to bind lymphocytes and certain tumor cells and on inflamed blood vessel endothelium it can mediate adhesion of lymphocytes, granulocytes and monocytes [8,11]. In vitro analyses have indicated it to be important in the transmigration step during the leukocyte extravasation process [12].Clever-1/Stabilin-1 is involved in two intracellular trafficking pathways, namely in receptor mediated endocytosis and recycling as well as in shuttling between endosomal compartment and trans-Golgi network. These complex mechanisms require interactions with several molecules ...

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Section: In Vitro Binding Assaysmentioning

confidence: 99%

Clever‐1/Stabilin‐1 regulates lymphocyte migration within lymphatics and leukocyte entrance to sites of inflammation

et al. 2009

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“…However, the molecular mechanisms involved in lymphocyte entrance into afferent lymphatics and exit from lymph nodes via efferent lymphatics are largely unknown. Very recently we found that mannose receptor on lymphatic endothelium supports lymphocyte binding to lymphatic vessels in an L-selectin-dependent fashion [14]. The involvement of sphingosine-1-phosphate receptor in lymphocyte exit from lymph nodes has also been shown [15].…”

Section: Introductionmentioning

confidence: 99%

The same endothelial receptor controls lymphocyte traffic both in vascular and lymphatic vessels

et al. 2003

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The mechanisms controlling the exit of lymphocytes from tissues via lymphatics are practically unknown. We have now identified a 270-300-kDa molecule designated common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) on human lymphatic endothelium and high endothelial venules. We show that it mediates binding of lymphocytes both to high endothelial venules and to lymphatic vessels. Moreover, blocking of the function of CLEVER-1 results in significant reduction of lymphocyte traffic in vivo. Notably, CLEVER-1 is also an inducible vascular adhesion molecule for other classes of leukocytes at sites of inflammation in peripheral tissues. These findings suggest that CLEVER-1 is involved in regulation of lymphocyte recirculation and migration of leukocytes to sites of inflammation and is a potential new target to control inflammation.

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“…Ex vivo. In principle the adhesion assays were performed as described earlier (26). The number of lymphocytes bound to SS and LS was counted under dark-field microscopy.…”

Section: Methodsmentioning

confidence: 99%

Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic

Iftakhar-E-Khuda

Fair-Mäkelä

Kukkonen-Macchi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, whereas efferent lymphatics allow only lymphocytes and antigens to leave the nodes. Despite the fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, the molecular characteristics of these different arms of the lymphatic vasculature are largely unknown. The objective of this work was to explore molecular differences behind the distinct functions of afferent and efferent lymphatic vessels, and find possible molecules mediating lymphocyte traffic. We used laser-capture microdissection and cell sorting to isolate lymphatic endothelial cells (LECs) from the subcapsular sinus (SS, afferent) and lymphatic sinus (LS, efferent) for transcriptional analyses. The results reveal marked differences between afferent and efferent LECs and identify molecules on lymphatic vessels. Further characterizations of Siglec-1 (CD169) and macrophage scavenger receptor 1 (MSR1/CD204), show that they are discriminatively expressed on lymphatic endothelium of the SS but not on lymphatic vasculature of the LS. In contrast, endomucin (EMCN) is present on the LS endothelium and not on lymphatic endothelium of the SS. Moreover, both murine and human MSR1 on lymphatic endothelium of the SS bind lymphocytes and in in vivo studies MSR1 regulates entrance of lymphocytes from the SS to the lymph node parenchyma. In conclusion, this paper reports surprisingly distinct molecular profiles for afferent and efferent lymphatics and a function for MSR1. These results may open avenues to explore some of the now-identified molecules as targets to manipulate the function of lymphatic vessels.lymphatics | cell traffic | lymphocytes | endothelium

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Mannose Receptor Is a Novel Ligand for L-Selectin and Mediates Lymphocyte Binding to Lymphatic Endothelium

Cited by 143 publications

References 37 publications

Clever‐1/Stabilin‐1 regulates lymphocyte migration within lymphatics and leukocyte entrance to sites of inflammation

Clever‐1/Stabilin‐1 regulates lymphocyte migration within lymphatics and leukocyte entrance to sites of inflammation

The same endothelial receptor controls lymphocyte traffic both in vascular and lymphatic vessels

Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic

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