scholarly journals Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning

2009 ◽  
Vol 207 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Trung H.M. Pham ◽  
Peter Baluk ◽  
Ying Xu ◽  
Irina Grigorova ◽  
Alex J. Bankovich ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
Sphingosine Kinase ◽  
Peyer's Patches ◽  
Cell Junctions ◽  
Peyer’S Patches ◽  
Cellular Source ◽  
Lymphocyte Egress

Lymphocyte egress from lymph nodes (LNs) is dependent on sphingosine-1-phosphate (S1P), but the cellular source of this S1P is not defined. We generated mice that expressed Cre from the lymphatic vessel endothelial hyaluronan receptor 1 (Lyve-1) locus and that showed efficient recombination of loxP-flanked genes in lymphatic endothelium. We report that mice with Lyve-1 CRE-mediated ablation of sphingosine kinase (Sphk) 1 and lacking Sphk2 have a loss of S1P in lymph while maintaining normal plasma S1P. In Lyve-1 Cre+ Sphk-deficient mice, lymphocyte egress from LNs and Peyer's patches is blocked. Treatment with pertussis toxin to overcome Gαi-mediated retention signals restores lymphocyte egress. Furthermore, in the absence of lymphatic Sphks, the initial lymphatic vessels in nonlymphoid tissues show an irregular morphology and a less organized vascular endothelial cadherin distribution at cell–cell junctions. Our data provide evidence that lymphatic endothelial cells are an in vivo source of S1P required for lymphocyte egress from LNs and Peyer's patches, and suggest a role for S1P in lymphatic vessel maturation.

scholarly journals Rapid G protein-regulated activation event involved in lymphocyte binding to high endothelial venules.

1993 ◽  
Vol 178 (1) ◽  
pp. 367-372 ◽  
Author(s):  
R F Bargatze ◽  
E C Butcher
Keyword(s):  
G Protein ◽  
Pertussis Toxin ◽  
Critical Role ◽  
Lymphocyte Activation ◽  
Inhibitory Effect ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
High Endothelial Venules ◽  
Activation Event

The homing of blood borne lymphocytes into lymph nodes and Peyer's patches is mediated in part by recognition and binding to specialized high endothelial venules (HEV). Here we demonstrate that a rapid pertussis toxin-sensitive lymphocyte activation event can participate in lymphocyte recognition of HEV. In situ video microscopic analyses of lymphocyte interactions with HEV in exteriorized mouse Peyer's patches reveal that pertussis toxin has no effect on an initial "rolling" displayed by many lymphocytes, but inhibits an activation-dependent "sticking" event required for lymphocyte arrest. This is the first demonstration that physiologic lymphocyte-endothelial interactions can involve sequential rolling, activation, and activation-dependent arrest, previously shown only for neutrophils. The inhibitory effect of the toxin is dependent on its G protein-modifying ADP-ribosyltransferase activity and can be reversed by phorbol myristic acetate, which bypasses cell surface receptors to trigger activation-dependent adhesion. Lymphocyte sticking can occur within 1-3 s after initiation of rolling. We conclude that a rapid receptor-mediated activation event involving G protein signaling can trigger stable lymphocyte attachment to HEV in vivo, and may play a critical role in regulating lymphocyte homing.

Abstract 27: ApoA-I Improves Lymphatic Function Through a Platelet-Dependent Mechanism in Atherosclerotic Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
François Dallaire ◽  
Gabriel Jean ◽  
Jean-Claude Tardif ◽  
Yahye Merhi ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Lymphatic Transport ◽  
Lv Function ◽  
Experimental Conditions ◽  
Lymphatic Function ◽  
Beneficial Effects ◽  
Dependent Mechanism

Rationale: Lymphatic vessels (LVs) are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and a particular attention has been brought on the role of the collecting LVs in early atherosclerosis-related lymphatic dysfunction. Whereas recent findings revealed that apoA-I restores the neovascularization capacity of the lymphatic system during tumor necrosis factor-induced inflammation, the effect of apoA-I on collecting LV function during atherosclerosis has not been tested. Objective: In the present study, we address whether and how apoA-I can enhance collecting LV function in atherosclerosis-associated lymphatic dysfunction. Methods and Results: A 6-week systemic treatment with lipid-free apoA-I enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr –/– mice when compared to control. As injection of apoA-I has been shown to protect wild-type mice against flow restriction-induced thrombosis, and that platelets are identified as key elements in the maintenance of lymphatic vessel integrity via their interaction with lymphatic endothelial cells (LECs), we have tested whether the effects of apoA-I could be mediated through a platelet-dependent mechanism. Our in vivo results show that apoA-I kinetics in lymph reflected that of blood. Ex vivo experiments performed with washed platelets isolated from mouse blood reveal that apoA-I decreased thrombin-induced but not podoplanin-induced platelet aggregation. Whereas this result suggests that apoA-I limits platelet thrombotic potential in blood but not in lymph, we demonstrate that treatment of human LECs with apoA-I increases the adhesion of bridge-like platelets on human LECs. Conclusions: Our results suggest that apoA-I can mediate beneficial effects on lymphatic function by promoting platelet adhesion to the lymphatic endothelium and consequently restore collecting LV integrity. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

scholarly journals Eosinophilia in transgenic mice expressing interleukin 5.

1990 ◽  
Vol 172 (5) ◽  
pp. 1425-1431 ◽  
Author(s):  
L A Dent ◽  
M Strath ◽  
A L Mellor ◽  
C J Sanderson
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Lymph Nodes ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Mesenteric Lymph Nodes ◽  
Gene Encoding ◽  
Interleukin 5

Experiments in vitro suggest that although interleukin 5 (IL-5) stimulates the late stages of eosinophil differentiation, other cytokines are required for the generation of eosinophil progenitor cells. In this study transgenic mice constitutively expressing the IL-5 gene were established using a genomic fragment of the IL-5 gene coupled to the dominant control region from the gene encoding human CD2. Four independent eosinophilic transgenic lines have thus far been established, two of which with 8 and 49 transgene copies, are described in detail. These mice appeared macroscopically normal apart from splenomegaly. Eosinophils were at least 65- and 265-fold higher in blood from transgenics, relative to normal littermates, and approximately two- or sevenfold more numerous relative to blood from mice infected with the helminth Mesocestoides corti. Much more modest increases in blood neutrophil, lymphocyte, and monocyte numbers were noted in transgenics, relative to normal littermates (less than threefold). Thus IL-5 in vivo is relatively specific for the eosinophil lineage. Large numbers of eosinophils were present in spleen, bone marrow, and peritoneal exudate, and were highest in the line with the greatest transgene copy number. Eosinophilia was also noted in histological sections of transgenic lungs, Peyer's patches, mesenteric lymph nodes, and gut lamina propria but not in other tissues examined. IL-5 was detected in the sera of transgenics at levels comparable to those seen in sera from parasite-infected animals. IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF) were not found. IL-5 mRNA was detected in transgenic thymus, Peyer's patches, and superficial lymph nodes, but not in heart, liver, brain, or skeletal muscle or in any tissues from nontransgenics. Bone marrow from transgenic mice was rich in IL-5-dependent eosinophil precursors. These data indicate that induction of the IL-5 gene is sufficient for production of eosinophilia, and that IL-5 can induce the full pathway of eosinophil differentiation. IL-5 may therefore not be restricted in action to the later stages of eosinophil differentiation, as suggested by earlier in vitro studies.

scholarly journals Association of Lactobacillus spp. with Peyer's Patches in Mice

2001 ◽  
Vol 8 (2) ◽  
pp. 320-324 ◽  
Author(s):  
Laura Plant ◽  
Patricia Conway
Keyword(s):  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Adhesion Assay ◽  
Scanning Electron Micrographs ◽  
Intestinal Tissue ◽  
High Adhesion ◽  
Preferential Binding ◽  
Scanning Electron

ABSTRACT Sixteen strains of Lactobacillus isolated from humans, mice, and food products were screened for their capacity to associate with Peyer's patches in mice. In preliminary experiments, in vitro binding to tissue pieces was assessed by scanning electron microscopy, and it was demonstrated qualitatively that 5 of the 16 strains showed some affinity for the Peyer's patches, irrespective of their association with the nonlymphoid intestinal tissue. Lactobacillus fermentum KLD was selected for further study, since, in addition to its intrinsically high adhesion rate, this organism was found to exhibit a preferential binding to the follicle-associated epithelium of the Peyer's patches compared with its level of binding to the mucus-secreting regions of the small intestine. Quantitative assessment of scanning electron micrographs of tissue sections which had been incubated with L. fermentum KLD or a nonbinding control strain, Lactobacillus delbruckii subsp.bulgaricus, supported these observations, since a marked difference in adhesion was noted (P < 0.05). This preferential association of strain KLD with the Peyer's patches was also confirmed with radiolabeled lactobacilli incubated with intestinal tissue in the in vitro adhesion assay. Direct recovery of L. fermentum KLD from washed tissue following oral dosing of mice revealed a distinct association (P < 0.05) between this organism and the Peyer's patch tissue. In contrast, L. delbruckii subsp. bulgaricus showed negligible binding to both tissue types in both in vitro and in vivo adhesion assays. It was concluded that L. fermentum KLD bound preferentially to Peyer's patches of BALB/c mice.

T Cell Trafficking in Acute GVHD: In Vivo Bioluminescence Evaluation To Elucidate the Role of Different Lymphatic Organs.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 593-593
Author(s):  
Andreas Beilhack ◽  
Stephan Schulz ◽  
Jeanette Baker ◽  
Georg F. Beilhack ◽  
Courtney B. Wieland ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymphoid Organs ◽  
The Body ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Alloreactive T Cells ◽  
Donor T Cells ◽  
Specific Priming

Abstract To study the complex pathophysiology of aGvHD in allogeneic hematopoietic cell transplantation (HCT) we transplanted transgenic luciferase expressing T cell populations into lethally irradiated HCT recipients (murine MHC major mismatch model, H-2q into H-2d). Tracking of light emitting donor T cells in living animals and detailed studies by multi color immunofluorescence microscopy (IFM) and FACS revealed the tight links of spatial and temporal evolution in this complex immune process. Donor derived T cells migrate to T cell areas in lymphoid tissues within a period of 12 hours. In the initial periods donor CD4+ T cells appear first with CD8+ T cell infiltration at later time points. Donor T cells start proliferating in lymphatic tissues on day 2 after transfer, as observed by BrdU stainings. Although alloreactive T cells are similarly activated in all lymphoid organs, they only up-regulate gut homing molecules after more than 5 cell divisions (CFSE proliferation analysis by FACS) in certain lymphoid organs (Peyer’s patches, mesenteric LN and spleen). Abruptly on day 4 after HCT, T cells migrate into intestinal sites. These findings strongly suggested, that specific priming sites are required for alloreactive T cells to induce a distinct type of tissue tropism in GvHD. In contrast to previous reports peformed without host conditioning, depletion of certain lymphoid organs (e.g. Peyer’s patches) before HCT or antibody blocking experiments did not control aGVHD. BLI showed, that anti-L-selectin or anti-MAdCAM-1 antibody treatment alone or in combination was effective in blocking donor T cell migration to lymph nodes and Peyer’s patches, while redirecting these cells to liver and spleen. Subsequently cells proliferated predominantly in the spleen until day 3 after HCT. Surprisingly we observed a full picture of gut infiltration on day 4 and skin involvement on day 5–6, similar in dynamics and strength to the aGvHD isotype control group. These findings demonstrated, that other lymphoid organs can functionally compensate for inducing gut and skin homing of alloreactive T cells. Of importance, we demonstrated that T cells that lacked homing molecules for secondary lymphoid organs had alloreactive properties in vitro, yet did not cause aGVHD in vivo. In summary, the activation of alloreactive T cells in specific sites throughout the body is complex and involves the acquisition of homing molecule expression. Transplantation of T cells with defined homing properties therefore, appears to be a promising alternative in conferring protective immunity early after HCT without the risk of aGvHD.

Listerial invasion protein internalin B promotes entry into ileal Peyer's patches in vivo

2011 ◽  
Vol 55 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Sayuri Chiba ◽  
Takeshi Nagai ◽  
Toshiyuki Hayashi ◽  
Yukiko Baba ◽  
Shigenori Nagai ◽  
...  
Keyword(s):  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Internalin B

scholarly journals S1P-S1PR1 activity controls VEGF-A signaling during lymphatic vessel development

2019 ◽  
Author(s):  
AM Golding-Ochsenbein ◽  
S Vidal ◽  
B Wilmering Wetter ◽  
C Guibourdenche ◽  
C Beerli ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Signaling Crosstalk ◽  
Balanced Growth ◽  
Sphingosine 1 Phosphate ◽  
Genetic Deletion ◽  
Vessel Development ◽  
Perinuclear Area

AbstractSphingosine-1-phosphate (S1P), a lipid signaling molecule produced by endothelial cells, is required for development and homeostasis of blood vessels. However, its role during lymphatic vessel development is unclear. We show in murine newborns that pharmacologically enhanced S1P signaling increases VEGF-A-dependent LEC proliferation. In contrast, S1PR1 inhibition, mediated by the antagonist NIBR0213 or LEC-specific genetic deletion of S1pr1, promotes filopodia formation and vessel branching, independent of VEGF-A. To investigate the S1P and VEGF-A signaling crosstalk observed in vivo, we used LECs cultured in vitro. We demonstrate that S1P activates endogenous S1PR1 in a constitutive, autocrine manner. Importantly, S1P-S1PR1 activity was required for VEGF-A-induced LEC proliferation and strongly supported ERK1/2 activation and VEGFR-2 trafficking to the perinuclear area. In conclusion, S1P-S1PR1 signaling promotes VEGF-A-dependent LEC proliferation and limits migratory and filopodia-forming responses. Hence, S1P-S1PR1 signaling is required for balanced growth factor-induced lymphangiogenesis and correctly patterned lymphatic vessels during postnatal development.

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