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A Mouse Model of Vascularized Heterotopic Spleen Transplantation for Studying Spleen Cell Biology and Transplant Immunity

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Local lymphogenic migration pathway in normal mouse spleen.

Kazuhiko Shimizu¹, Shunichi Morikawa, Shuji Kitahara

¹Department of Anatomy and Developmental Biology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Cell and Tissue Research

|November 10, 2009

Summary

This study reveals novel lymphatic vessels in the spleen, crucial for immune cell transport. These vessels, alongside unique meshworks, facilitate spleen cell traffic, complementing the blood circulatory system.

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Area of Science:

Immunology
Vascular Biology
Spleen Anatomy

Background:

The spleen's immunological and hemodynamic roles are significant, yet its lymphatic vasculature remains poorly understood.
Limited research exists on the detailed structure and function of splenic lymphatic vessels.

Purpose of the Study:

To characterize the lymphatic vessels within the normal mouse spleen using advanced imaging techniques.
To elucidate the spatial relationship between splenic lymphatic vessels and the blood vascular system.
To investigate the role of splenic lymphatic vessels and associated structures in immune cell trafficking.

Main Methods:

Utilized immunohistochemical three-dimensional imaging with lymphatic markers (LYVE-1, VEGFR-3, podoplanin).
Examined the localization and morphology of lymphatic vessels relative to blood vessels.
Tracked the movement of fluorescently labeled lymphocytes (GFP(+)) within the spleen and to lymph nodes.

Main Results:

Identified LYVE-1-positive lymphatic vessels running counter to arterial flow along central and trabecular arteries, exiting at the hilum.
Characterized these vessels as collecting lymphatic vessels due to surrounding type IV collagen.
Discovered podoplanin-positive stromal cell meshworks surrounding lymphatic vessels and central arteries, facilitating rapid lymphocyte accumulation and transport.

Conclusions:

Splenic lymphatic vessels and associated podoplanin-positive meshworks play a critical role in immune cell traffic.
These structures provide an extravascular pathway for lymphocytes, complementing blood circulation.
The findings offer new insights into spleen function and immune cell dynamics.