Macrophage mannose receptor on lymphatics controls cell trafficking

• Published in: Blood 2008-07, Vol.112 (1), p.64-72
• Main Authors: Marttila-Ichihara, Fumiko, Turja, Raisa, Miiluniemi, Mari, Karikoski, Marika, Maksimow, Mikael, Niemelä, Jussi, Martinez-Pomares, Luisa, Salmi, Marko, Jalkanen, Sirpa
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation; Antigens, Neoplasm; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Biological and medical sciences; Cell Adhesion; Cell Line, Tumor; Cell Movement; Dendritic Cells - immunology; Dendritic Cells - pathology; Dissemination; Female; Host-tumor relations. Immunology. Biological markers; Lectins, C-Type - deficiency; Lectins, C-Type - genetics; Lectins, C-Type - physiology; Lymphatic Metastasis; Lymphatic System - cytology; Lymphatic System - physiology; Macrophages - immunology; Macrophages - physiology; Male; Mannose-Binding Lectins - deficiency; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - physiology; Medical sciences; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - secondary; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Cell Surface - deficiency; Receptors, Cell Surface - genetics; Receptors, Cell Surface - physiology; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Tumor cell; Tumors
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-10-118984

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.