The Primary Valves in the Initial Lymphatics during Inflammation

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Abstract
Background: The primary valve system in the initial lymphatics prevents fluid transport from the initial lymphatics back into the interstitium. The authors hypothesize that since the primary valves are made up of an extraordinarily thin endothelium, they are readily compromised by mechanical or biochemical inflammatory stimuli. Thus, the opening dimension of the primary valves and their ability to prevent reflux into the interstitium during inflammation were investigated. Methods and Results: Acute inflammation was generated in the intact rat spinotrapezius muscle by suffusion of f-Met-Leu-Phe and platelet-activating factor. Once inflamed, the effective opening dimensions of the primary valves and the transport back out of the initial lymphatics were determined by examining the transport of fluorescent tracers from the interstitium to the lymphatics. Quantum dots and fluorescently labeled albumin readily enter initial lymphatics from the interstitium. The maximum diameter of microspheres that enter the initial lymphatics is between 0.5 μm and 0.8 μm in both control and inflamed tissue. While under control conditions no quantum dots escaped from initial lymphatics back into the interstitium, during inflammation there was extensive escape of quantum dots. Conclusions: These results suggest that, in acute inflammation, the function of the endothelial barriers in the initial lymphatics may be compromised. A failure of the primary lymphatic valves has two consequences. First, fluid clearance from the tissue is less efficient, which causes the level of edema to increase. Second, the leaking initial lymphatics allow inflammatory mediators to accumulate in the tissue, therefore enhancing interstitial and lymphatic inflammatory reactions.