Macrophage mannose receptor on lymphatics controls cell trafficking

Marttila-Ichihara, Fumiko; Turja, Raisa; Miiluniemi, Mari; Karikoski, Marika; Maksimow, Mikael; Niemelä, Jussi; Martı́nez-Pomares, Luisa; Salmi, Marko; Jalkanen, Sirpa

doi:10.1182/blood-2007-10-118984

Cited by 91 publications

(79 citation statements)

References 41 publications

(44 reference statements)

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“…the injected lymphocytes have had enough time to enter into the draining lymph nodes and most of them have not yet left the node via efferent lymphatics) [17,18]. We first used our function-blocking anti-human Clever-1/Stabilin-1 Ab that cross-reacts with the rabbit homolog [8,12].…”

Section: Resultsmentioning

confidence: 99%

“…Only few molecules present on afferent lymphatics such as macrophage mannose receptor, sphingosine-1-phosphate receptor and CCL21 have been shown to mediate lymphocyte traffic via afferent lymphatic vessels [18]. Among those, Clever-1/Stabilin-1 is the first one, which is now shown to also be a good target at sites of inflammation in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…The recycling nature of Clever-1/Stabilin-1 also fits well to this idea, especially when the cells are transmigrating via the transcellular route. Moreover, our in vivo results together with earlier in vitro adhesion results indicate that adhesion is a critical step in lymphocyte migration into the afferent lymphatics and its inhibition leads to diminished lymphocyte traffic into the draining lymph nodes.Only few molecules present on afferent lymphatics such as macrophage mannose receptor, sphingosine-1-phosphate receptor and CCL21 have been shown to mediate lymphocyte traffic via afferent lymphatic vessels [18]. Among those, Clever-1/Stabilin-1 is the first one, which is now shown to also be a good target at sites of inflammation in vivo.…”

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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: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2009

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“…Van et al (2006) recently reported a requirement for DC expression of CD47 for successful homing, although the mechanism remains unknown. In addition, lymphatic endothelial cell expression of macrophage mannose receptor (Marttila-Ichihara et al 2008) and CLEVER-1 (Salmi et al 2004) has been identiWed to mediate lymphocyte binding, although a role in DC migration has yet to be determined. Sphingosine-1-phosphate is required for T cell entry into lymphatics (Ledgerwood et al 2008), but its function in DC emigration is yet to be evaluated.…”

Section: Other Moleculesmentioning

confidence: 99%

Visualizing dendritic cell migration within the skin

Roediger

Smith

et al. 2008

Histochem Cell Biol

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Dendritic cells (DCs) within the skin are a heterogeneous population of cells, including Langerhans cells of the epidermis and at least three subsets of dermal DCs. Collectively, these DCs play important roles in the initiation of adaptive immune responses following antigen challenge of the skin as well as being mediators of tolerance to self-antigen. A key functional aspect of cutaneous DCs is their migration both within the skin and into lymphatic vessels, resulting in their emigration to draining lymph nodes. Here, we discuss our current understanding of the requirements for successful DC migration in and from the skin, and introduce some of the microscopic techniques developed in our laboratory to facilitate a better understanding of this process. In particular, we detail our current use of multi-photon excitation (MPE) microscopy of murine skin to dissect the migratory behavior of DCs in vivo.

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“…Molecules such as lymphatic vessel endothelial hyaluronan receptor-1 (Lyve-1), podoplanin, vascular endothelial growth factor receptor-3 (VEGFR-3), and prospero homeobox 1 (PROX1), which discriminate lymphatic from blood vessel endothelium are expressed at roughly comparable levels both on afferent and efferent lymphatics in human (2). Moreover, molecules known to participate in physiological cell trafficking such as sphingosine-1-phosphate receptor, macrophage mannose receptor, and Clever-1/ Stabilin-1 act both on the afferent and efferent arms of the lymphatic vasculature (3)(4)(5)(6). Functionally afferent and efferent lymphatics have a fundamental difference: most leukocytes can enter the LN via the afferent lymphatics, but only lymphocytes can exit the nodes via the efferent lymphatics under steady-state conditions.…”

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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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Macrophage mannose receptor on lymphatics controls cell trafficking

Cited by 91 publications

References 41 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

Visualizing dendritic cell migration within the skin

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

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