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 Blood, 1 July 2008, Vol. 112, No. 1, pp. 64-72.
Prepublished online as a Blood First Edition Paper on April 23, 2008; DOI 10.1182/blood-2007-10-118984.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Macrophage mannose receptor on lymphatics controls cell trafficking

Fumiko Marttila-Ichihara1, Raisa Turja1,*, Mari Miiluniemi1,*, Marika Karikoski1,2, Mikael Maksimow1, Jussi Niemelä1, Luisa Martinez-Pomares3, Marko Salmi1, and Sirpa Jalkanen1

1 MediCity Research Laboratory and Department of Medical Microbiology, Turku University and National Public Health Institute, Turku, Finland; 2 Turku Graduate School of Biomedical Sciences, Turku, Finland; and 3 School of Molecular Medical Sciences, Institute of Infection Immunity and Inflammation, Queen's Medical Centre, University of Nottingham, Nottingham, United Kingdom

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.


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