scholarly journals A Novel Migration Pathway for Rat Dendritic Cells from the Blood: Hepatic Sinusoids–Lymph Translocation

1997 ◽  
Vol 185 (4) ◽  
pp. 777-784 ◽  
Author(s):  
Shunsuke Kudo ◽  
Kenjiro Matsuno ◽  
Taichi Ezaki ◽  
Michio Ogawa
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Kupffer Cells ◽  
Lymphoid Tissues ◽  
Proliferating Cells ◽  
High Endothelial Venules ◽  
Regional Lymph Nodes ◽  
Migration Pathway ◽  
Migration Pathways

The migration pathways for dendritic cells (DC) from the blood are not yet completely resolved. In our previous study, a selective recruitment of DC progenitors from the blood to the liver was suggested. To clarify the role of the hepatic sinusoids in the migration of blood DC, relatively immature DC and mature DC were isolated from hepatic and intestinal lymph, and intravenously transferred to allogeneic hosts. It was then possible to detect small numbers of DC within secondary lymphoid tissues either by immunostaining for donor type major histocompatibility complex class I antigen or, at much higher sensitivity, for bromodeoxyuridine incorporated by proliferating cells (mainly T lymphocytes), which responded to the alloantigen presented by the administered DC. The intravenously injected DC accumulated in the paracortex of regional lymph nodes of the liver via a lymph-borne pathway. Intravenously injected fluorochrome-labeled syngeneic DC behaved similarly. In contrast, very few DC were found in spleen sections and were hardly detectable in other lymph nodes or in other tissues. An in situ cell binding assay revealed a significant and selective binding of DC to Kupffer cells in liver cryosections. It is concluded that rat DC can undergo a blood–lymph translocation via the hepatic sinusoids, but not via the high endothelial venules of lymph nodes. Hence the hepatic sinusoids may act as a biological concentrator of blood DC into the regional hepatic nodes. Kupffer cells may play an important role in this mechanism.

scholarly journals Role of CCR8 and Other Chemokine Pathways in the Migration of Monocyte-derived Dendritic Cells to Lymph Nodes

2004 ◽  
Vol 200 (10) ◽  
pp. 1231-1241 ◽  
Author(s):  
Chunfeng Qu ◽  
Emmerson W. Edwards ◽  
Frank Tacke ◽  
Véronique Angeli ◽  
Jaime Llodrá ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Chemokine Receptors ◽  
Human Monocyte ◽  
Monocyte Subsets ◽  
Migration Pathways

Studying the influence of chemokine receptors (CCRs) on monocyte fate may reveal information about which subpopulations of monocytes convert to dendritic cells (DCs) and the migration pathways that they use. First, we examined whether prominent CCRs on different monocyte subsets, CCR2 or CX3CR1, mediated migration events upstream of the accumulation of monocyte-derived DCs in lymph nodes (LNs). Monocytes were labeled and traced by uptake of latex microspheres in skin. Unexpectedly, neither CCR2 nor CX3CR1 were required. However, absence of CCR2 led to an increased labeling of the minor Gr-1int monocyte population, and the number of latex+ DCs that emigrated to LNs was correspondingly increased. Characterization of Gr-1int monocytes revealed that they selectively expressed CCR7 and CCR8 mRNA in blood. CCR7 and CCR8 pathways were used by monocyte-derived DCs during mobilization from skin to LNs. The role of CCR8 in emigration from tissues also applied to human monocyte-derived cells in a model of transendothelial trafficking. Collectively, the data suggest that Gr-1int monocytes may be most disposed to become a lymphatic-migrating DCs. When these monocyte-derived DCs exit skin to emigrate to LNs, they use not only CCR7 but also CCR8, which was not previously recognized to participate in migration to LNs.

scholarly journals Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin

2005 ◽  
Vol 201 (4) ◽  
pp. 509-515 ◽  
Author(s):  
William Vermi ◽  
Elena Riboldi ◽  
Valerie Wittamer ◽  
Francesca Gentili ◽  
Walter Luini ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lupus Erythematosus ◽  
Normal Skin ◽  
Cell Monolayer ◽  
Lymphoid Organs ◽  
High Endothelial Venules ◽  
Luminal Side ◽  
Plasmacytoid Dcs ◽  
Secondary Lymphoid Organs

Chemerin is a chemotactic agent that was recently identified as the ligand of ChemR23, a serpentine receptor expressed by activated macrophages and monocyte-derived dendritic cells (DCs). This paper shows that blood plasmacytoid and myeloid DCs express functional ChemR23. Recombinant chemerin induced the transmigration of plasmacytoid and myeloid DCs across an endothelial cell monolayer. In secondary lymphoid organs (lymph nodes and tonsils), ChemR23 is expressed by CD123+ plasmacytoid DCs and by CD1a+ DC-SIGN+ DCs in the interfollicular T cell area. ChemR23+ DCs were also observed in dermis from normal skin, whereas Langerhans cells were negative. Chemerin expression was selectively detected on the luminal side of high endothelial venules in secondary lymphoid organs and in dermal endothelial vessels of lupus erythematosus skin lesions. Chemerin+ endothelial cells were surrounded by ChemR23+ plasmacytoid DCs. Thus, ChemR23 is expressed and functional in plasmacytoid DCs, a property shared only by CXCR4 among chemotactic receptors. This finding, together with the selective expression of the cognate ligand on the luminal side of high endothelial venules and inflamed endothelium, suggests a key role of the ChemR23/chemerin axis in directing plasmacytoid DC trafficking.

scholarly journals Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, α4β1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways

2003 ◽  
Vol 197 (10) ◽  
pp. 1255-1267 ◽  
Author(s):  
Baohui Xu ◽  
Norbert Wagner ◽  
Linh Nguyen Pham ◽  
Vincent Magno ◽  
Zhongyan Shan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Lymphocyte Migration ◽  
High Endothelial Venules ◽  
Level Of Involvement ◽  
Selectin Ligand ◽  
High Level ◽  
Migration Pathways ◽  
B And T Lymphocytes

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–α4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. α4β7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against α4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of α4β1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues.

scholarly journals Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5875-5884 ◽  
Author(s):  
Hideaki Tanizaki ◽  
Gyohei Egawa ◽  
Kayo Inaba ◽  
Tetsuya Honda ◽  
Saeko Nakajima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Actin Polymerization ◽  
Cell Stimulation ◽  
T Cell Stimulation ◽  
Acquired Immune Responses

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

scholarly journals A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane

2021 ◽  
Vol 11 ◽  
Author(s):  
Itai Margulis ◽  
Inna Naroditsky ◽  
Miriam Gross-Cohen ◽  
Neta Ilan ◽  
Israel Vlodavsky ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Lymph Nodes ◽  
Nuclear Membrane ◽  
Tumor Metastasis ◽  
Cellular Localization ◽  
Thyroid Tissue ◽  
Clinicopathological Parameters ◽  
Regional Lymph Nodes ◽  
Normal Thyroid

Activity of the endo-beta-glucuronidase heparanase, capable of cleaving heparan sulfate (HS), is most often elevated in many types of tumors, associating with increased tumor metastasis and decreased patients’ survival. Heparanase is therefore considered to be a valid drug target, and heparanase inhibitors are being evaluated clinically in cancer patients. Heparanase 2 (Hpa2) is a close homolog of heparanase that gained very little attention, likely because it lacks HS-degrading activity typical of heparanase. The role of Hpa2 in cancer was not examined in detail. In head and neck cancer, high levels of Hpa2 are associated with decreased tumor cell dissemination to regional lymph nodes and prolonged patients’ survival, suggesting that Hpa2 functions to attenuate tumor growth. Here, we examined the role of Hpa2 in normal thyroid tissue and in benign thyroid tumor, non-metastatic, and metastatic papillary thyroid carcinoma (PTC) utilizing immunostaining in correlation with clinicopathological parameters. Interestingly, we found that Hpa2 staining intensity does not significantly change in the transition from normal thyroid gland to benign, non-metastatic, or metastatic thyroid carcinoma. Remarkably, we observed that in some biopsies, Hpa2 is accumulating on the membrane (envelop) of the nucleus and termed this cellular localization NM (nuclear membrane). Notably, NM localization of Hpa2 occurred primarily in metastatic PTC and was associated with an increased number of positive (metastatic) lymph nodes collected at surgery. These results describe for the first time unrecognized localization of Hpa2 to the nuclear membrane, implying that in PTC, Hpa2 functions to promote tumor metastasis.

scholarly journals P01.11 Role of exosomes as promotors or biomarkers to study activation of leukemia-derived dendritic cells (DCleu)-mediated antileukemic activation of adaptive and innate immune-reactive cells against AML-blasts

2020 ◽  
Vol 8 (Suppl 2) ◽  
pp. A13.2-A14
Author(s):  
L Li ◽  
V Mussack ◽  
E Pepeldjiyska ◽  
A Hartz ◽  
A Rank ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Healthy Volunteers ◽  
Information Transfer ◽  
Immune Monitoring ◽  
Lymphocyte Culture ◽  
Innate Immune ◽  
Proliferating Cells ◽  
Continuous Increase

BackgroundAntileukemic responses of immune reactive cells in AML-patients need to be improved. Combinations of blast-modulatory kitM (GM-CSF+PGE1) (vs control) convert myeloid blasts into dendritic cells of leukemic origin (DCleu), that effectively activate immune-cells against leukemic blasts. Exosomes are small (30–150 nm) membranous vesicles of endocytic origin produced by all cells under physiological and pathological conditions. Their involvement in nearly all aspects of malignant transformation has generated much interest in their biology, mechanisms responsible for information transfer and their role in immune-surveillance as well as -escape.Exosomes secreted by dendritic cells (DCs) have been shown to allow efficient activation of T lymphocytes, displaying potential as promoters of adaptive immune responses.Materials and Methods1)DC/DCleu-culture of blast containing AML patients’ whole blood (WB) (n=10) and of healthy volunteers(n=8) with kits, T-cell enriched mixed lymphocyte culture (MLC) with kit- vs un-treated WB, functional blast-cytotoxicity and, leukemia-specificity assays (Degranulation/intracellular cytokine-assays), Flowcytometric evaluation of blast-,DC- and lymphocyte composition before or after cultures. 2)Exosomes were isolated by immunoaffinity from serum, DC- and MLC-culture supernatants of 3 AML patients and 3 healthy volunteers. Exosomes were negatively stained and characterized by transmission electron microscopy (TEM). Fluorescence nanoparticle tracking analysis (fNTA) was performed to determine exosomal size and -concentration. Obtained results were compared in AML and healthy volunteers.ResultsAddition of kitM to blast-containing WB significantly increased frequencies of mature DC/DCleu and their subtypes compared to untreated WB without induction of blasts’ proliferation. Immune monitoring showed a continuous increase ofactivated/proliferating cells of the adaptive and innate immune system after Tcell-enriched MLC using kitM pretreated vs -untreated WB, suggesting a production/activation of (potentially leukemia-specific) cells after kit-stimulation. Moreover kit-pretreated WB regularly and significantly improved provision, activation as well as antileukemic and leukemia-specifically directed immune reactive cells after MLC. TEM showed exosome-like structures with a typically cup-shaped appearance without any differences between healthy and AML samples. fNTA revealed average vesicle sizes of 177±23 nm (healthy) and 178±17 nm (AML). Higher levels of EVs were detectable in AML samples compared to healthy controls in serum and after DC-culture, but lower levels after MLC independent of culture conditions.Interestingly, the number of EVs increased during cultivation of DC of AML and healthy samples, but not in AML-derived MLC samples.ConclusionsWe will provide data in AML patients and healthy volunteers about a potential role of DCs- and MLC-derived exosomes as biomarkers in immune responses, malignant progression or as potential therapeutic targets for AML patients.Disclosure InformationL. li: None. V. Mussack: None. E. Pepeldjiyska: None. A. Hartz: None. A. Rank: None. C. Schmid: None. E. Özkaya: None. S. Ugur: None. M. Pfaffl: None. H. Schmetzer: None.

scholarly journals Global vascular expression of murine CD34, a sialomucin-like endothelial ligand for L-selectin

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2554-2565 ◽  
Author(s):  
S Baumhueter ◽  
N Dybdal ◽  
C Kyle ◽  
LA Lasky
Keyword(s):  
Lymph Nodes ◽  
Immune Surveillance ◽  
Nod Mice ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
High Endothelial Venules ◽  
Endothelial Cell Surface ◽  
Vascular Expression

Abstract Extravasation of leukocytes into organized lymphoid tissues and into sites of inflammation is critical to immune surveillance. Leukocyte migration to peripheral lymph nodes (PLN), mesenteric lymph nodes (MLN) and Peyer's patches (PP) depends on L-selectin, which recognizes carbohydrate-bearing, sialomucin-like endothelial cell surface glycoproteins. Two of these ligands have been identified at the molecular level. One is the potentially soluble mucin, GlyCAM 1, which is almost exclusively produced by high endothelial venules (HEV) of PLN and MLN. The second HEV ligand for L-selectin is the membrane-bound sialomucin CD34. Historically, this molecule has been successfully used to purify human pluripotent bone marrow stem cells, and limited data suggest that human CD34 is present on the vascular endothelium of several organs. Here we describe a comprehensive analysis of the vascular expression of CD34 in murine tissues using a highly specific antimurine CD34 polyclonal antibody. CD34 was detected on vessels in all organs examined and was expressed during pancreatic and skin inflammatory episodes. A subset of HEV-like vessels in the inflamed pancreas of nonobese diabetic (NOD) mice are positive for both CD34 and GlyCAM 1, and bind to an L-selectin/immunoglobulin G (IgG) chimeric probe. Finally, we found that CD34 is present on vessels of deafferentiated PLN, despite the fact that these vessels are no longer able to interact with L-selectin or support lymphocyte binding in vitro or trafficking in vivo. Our data suggest that the regulation of posttranslational carbohydrate modifications of CD34 is critical in determining its capability to act as an L-selectin ligand. Based on its ubiquitous expression, we propose that an appropriately glycosylated form of vascular CD34 may act as a ligand for L-selectin-mediated leukocyte trafficking to both lymphoid and nonlymphoid sites.

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