Role of Lymphatic Endothelial Cell Caveolin-1 in Macromolecule Transport
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The lymphatic system is a network of capillaries, vessels, and nodes that span the length of our entire body. Lymphatic capillaries uptake immune cells, fluid, and macromolecules from the interstitium and transport this lymph through vessels to lymph nodes for immune regulation and tissue fluid balance ultimately returning it to the blood vasculature. How fluid and solutes enter lymphatic capillaries has long been viewed as a passive paracellular mechanism in which macromolecules and fluid enter through valve-like openings in the loosely overlapped cell-cell junctions of lymphatic capillaries. Recent studies have demonstrated that lymphatic endothelial cells (LECs) may utilize pore formation with membrane caveolae as an active transcellular pathway to uptake macromolecules from the interstitium. Caveolin-1 is a protein required for the formation of caveolae and transcellular transport processes. We hypothesized that LECs utilize active caveolae to regulate lymphatic solute transport. To allow us to test our hypothesis, methods for primary LEC isolations and lymphatic vessel isolations had to be developed, established, and successfully tested. To test our hypothesis, we utilized a transgenic mouse carrying loxP sites flanking exon 3 of the Cav-1 gene. When crossed with mice expressing the enzyme Cre recombinase specifically in LECs, we generated mice lacking caveolin-1 in lymphatic endothelium, and, therefore, LECs incapable of forming caveolae. We utilized this mouse to identify changes in lymphatic uptake and transport of macromolecules over a range of sizes in vivo. We isolated and perfused lymphatic vessels from these mice to quantify changes in vessel permeability as a function of solute size. In vitro, LECs from these mice, were cultured into monolayers to demonstrate active barrier function to macromolecules. Our data thus identify mechanisms of lymphatic transport that actively regulate solute transport with implications in antigen transport and immune maintenance.
Upchurch, Bradley Dean (2017). Role of Lymphatic Endothelial Cell Caveolin-1 in Macromolecule Transport. Undergraduate Research Scholars Program. Available electronically from