Macrophage mannose receptor on lymphatics controls cell trafficking

Area of Science:

• Immunology
• Cell Biology
• Oncology

Background:

• The macrophage mannose receptor (MR) is known to play roles in pathogen recognition, serum glycoprotein clearance, and antigen presentation.
• MR is also expressed on lymphatic endothelial cells, but its function in this context is largely uncharacterized.

Purpose of the Study:

• To investigate the role of the macrophage mannose receptor (MR) in leukocyte trafficking and cancer metastasis.
• To determine the function of MR expressed on lymphatic endothelial cells.

Main Methods:

• Utilized MR-deficient (MR(-/-)) and wild-type (WT) mice.
• Assessed lymphocyte migration from skin to draining lymph nodes.
• Evaluated primary tumor growth and lymph node metastasis in a tumor model.
• Quantified adhesion of lymphocytes and tumor cells to lymphatic vessels.

Main Results:

• Lymphocyte migration into draining lymph nodes was significantly reduced in MR(-/-) mice.
• Primary tumors were larger, but regional lymph node metastases were smaller in MR(-/-) mice compared to WT controls.
• Adhesion of lymphocytes and tumor cells to lymphatic vessels was decreased in MR(-/-) mice.
• Macrophage antigen presentation capabilities were similar between genotypes.

Conclusions:

• MR on lymphatic endothelial cells is crucial for leukocyte and tumor cell trafficking via afferent lymphatics.
• MR deficiency impacts cancer progression, reducing metastasis to regional lymph nodes.
• Targeting MR on lymphatic vasculature presents a potential therapeutic strategy for managing inflammation and cancer metastasis.