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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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Submitted October 17, 2007
Accepted March 18, 2008
Macrophage mannose receptor on lymphatics controls cell trafficking
Fumiko Marttila-Ichihara, Raisa Turja, Mari Miiluniemi, Marika Karikoski, Mikael Maksimow, Jussi Niemela, Luisa Martinez-Pomares, Marko Salmi, and Sirpa Jalkanen*
MediCity Research Laboratory and Department of Medical Micr, Turku University and National Public Health Institute, Turku, Finland
Turku Graduate School of Biomedical Science, Turku, Finland
School of Molecular Medical Sciences, Queen’s Medical Centr, University of Nottingham, Nottingham, United Kingdom
* Corresponding author; email: sirpa.jalkanen{at}utu.fi.
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, whilst 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. Ability of macrophages to present tumor antigens is indistinguishable between the two 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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