Article

Macrophage mannose receptor on lymphatics controls cell trafficking

MediCity Research Laboratory and Department of Medical Microbiology, Turku University and National Public Health Institute, Turku, Finland.
Blood (Impact Factor: 9.78). 08/2008; 112(1):64-72. DOI: 10.1182/blood-2007-10-118984
Source: PubMed

ABSTRACT Macrophage mannose receptor (MR) participates in pathogen recognition, clearance of endogenous serum glycoproteins, and antigen presentation. MR is also present on lymphatic vessels, where its function is unknown. Here we show that migration of lymphocytes from the skin into the draining lymph nodes through the afferent lymphatics is reduced in MR-deficient mice, while the structure of lymphatic vasculature remains normal in these animals. Moreover, in a tumor model the primary tumors grow significantly bigger in MR(-/-) mice than in the wild-type (WT) controls, whereas the regional lymph node metastases are markedly smaller. Adhesion of both normal lymphocytes and tumor cells to lymphatic vessels is significantly decreased in MR-deficient mice. The ability of macrophages to present tumor antigens is indistinguishable between the 2 genotypes. Thus, MR on lymphatic endothelial cells is involved in leukocyte trafficking and contributes to the metastatic behavior of cancer cells. Blocking of MR may provide a new approach to controlling inflammation and cancer metastasis by targeting the lymphatic vasculature.

0 Bookmarks
 · 
140 Views
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), a member of the C-type lectin superfamily, has been reported to bind to various pathogens and several tumor cells and to participate in immunoregulation. It is still unclear whether there is a significant association between the level of DC-SIGN and non-Hodgkin lymphoma (NHL). To investigate the clinical diagnostic significance of DC-SIGN in NHL, we conducted a study with 52 NHL patients and 104 healthy individuals. Enzyme-linked immunosorbent assay and tissue microarray technology were utilized for the analysis. The serum sDC-SIGN levels in the NHL patients were significantly lower than those in the healthy controls (P = 0.0019). A cutoff value of 1.499 µg/ml for sDC-SIGN predicted the presence of NHL with 78.85 % sensitivity and 53.85 % specificity [area under the curve (AUC) = 0.6531, P = 0.0019]. The serum sDC-SIGN levels in NHL patients were also significantly correlated with β2-microglobulin (P = 0.0062). Moreover, tissue microarray analysis demonstrated that the expression of DC-SIGN in the lymph nodes or tissues of 96 NHL patients was significantly lower than that in 18 normal lymph nodes (P < 0.0001). However, the expression of DC-SIGN in NHL displayed no significant correlation with the expression of CD20 or CD79a. In conclusion, DC-SIGN may be a promising biological molecule for clinical research on NHL, whereas the underlying roles need to be investigated in additional studies.
    Medical Oncology 10/2014; 31(10):202. DOI:10.1007/s12032-014-0202-6 · 2.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Current methods for sentinel lymph node (SLN) mapping involve the use of radioactivity-detection with technetium-99m sulfur colloid and/or visual-guided identification using a blue dye. To overcome the kinetic variations of two individual imaging agents through the lymphatic system, we report herein on two novel multi-functional macromolecules, 5a and 6a, that contain a radionuclide (99mTc or 68Ga) and a near infrared (NIR) reporter for pre- and/or intraoperative SLN mapping by nuclear and NIR optical imaging techniques. Both bimodal probes are dextran-based polymers (10 kDa) functionalized with pyrazole-diamine (Pz) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelating units for labeling with fac-[99mTc(CO)3]+ or 68Ga(III), respectively, mannose units for receptor targeting and NIR fluorophore units for optical imaging. The probes allowed a clear visualization of the popliteal node by single-photon emission computed tomography (SPECT/CT) or positron emission tomography (PET/CT) as well as real time optical-guided excision. Biodistribution studies confirmed that both macromolecules present a significant accumulation in the popliteal node (5a: 3.87 ± 0.63 % IA/organ; 6a: 1.04 ± 0.26 % IA/organ), with minimal spread to other organs. The multi-functional nanoplatforms display a popliteal extraction efficiency > 90 %, highlighting their potential to be further explored as dual imaging agents.
    Bioconjugate Chemistry 09/2014; 25(11). DOI:10.1021/bc500336a · 4.82 Impact Factor

Full-text (2 Sources)

Download
51 Downloads
Available from
May 19, 2014