Quantitation of changes in lymph protein concentration during lymph node transit

Abstract

Many investigators assume the protein concentration and colloid osmotic pressure of interstitial fluid and lymph to be identical even after the lymph has passed through a lymph node. We quantitated the degree of modification of lymph by the dog popliteal lymph node by perfusing isolated lymph nodes in situ at physiological flow rates with homologous plasma or plasma diluted to low protein concentration. This enabled us to compare directly prenodal and postnodal lymph flows and protein concentrations. When undiluted plasma was infused into the node, fluid filtered from the blood into the lymph, diluting the lymph. When diluted plasma was infused, fluid was absorbed from the lymph, concentrating the lymph. Nearly all (98%) of the change in lymph protein concentration could be explained by transfer of protein-free fluid either into or out of the lymph. However, when the nodes were perfused with lymph having a colloid osmotic pressure that exactly balanced the hydrostatic and osmotic forces acting across the lymph node blood-lymph barrier, the lymph was not modified during nodal transit. This "equilibrium colloid osmotic pressure" averaged 60% of that of plasma. The concentrating-diluting mechanism became more significant as the perfusion rate decreased and/or as the colloid osmotic pressure of the afferent lymph was made progressively greater than or less than the equilibrium colloid osmotic pressure. We conclude that lymph nodes modify lymph protein concentration and colloid osmotic pressure except when these are already at equilibrium values for given lymph node conditions. Therefore, the assumption that postnodal lymph is representative of interstitial fluid, especially at low but still physiological lymph flows, is likely to be incorrect.

Access to the Spleen Microenvironment through Lymph Shows Local Cytokine Production, Increased Cell Flux, and Altered Signaling of Immune Cells during Lipopolysaccharide-Induced Acute Inflammation

“…In the kidney, we found that albumin injected prenodally in a hilar lymph vessel was completely recovered in the thoracic duct (16). Since lymph node protein and fluid exchange decrease with increased flow (17), and the spleen lymph flow rates were on average ∼four times higher than that of the kidney, our kidney data suggest minimal exchange of fluid and proteins also in the spleen nodes. One way to show that spleen lymph was the dominant component in the collected lymph might have been to compare with thoracic duct lymph, which derives from the entire abdominal area (18).…”

CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability

“…Such lymph-migratory DCs, exquisitely dependent upon CCR7 for their trafficking to LNs, are known to regulate the maturation of the specialized postcapillary venules in LNs, the HEVs (3, 4, 7). From this perspective, it is interesting to note that classical studies on lymphatic collecting vessels in dogs, done in vivo with LNs remaining functional during collecting vessel cannulations, show a key role for LN venules in fluid exchange and lymph flow (35)(36)(37). Specifically, the venules in LNs are responsible for uptake of water during the appreciable concentration of afferent lymph before it traverses the LN and enters efferent lymph (35).…”

Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease

“…6 The permeability of the collecting vessels has recently been shown to be regulated by a subset of dendritic cells. 7 Furthermore, classic studies in dogs by Adair et al 8 revealed another means by which collecting lymphatic vessel hyperpermeability develops. They observed that afferent lymph, with its typical low protein content, is filtered in the LN so that water is absorbed into the venous vasculature and efferent lymph emerges nearly as concentrated as plasma.…”

“…They observed that afferent lymph, with its typical low protein content, is filtered in the LN so that water is absorbed into the venous vasculature and efferent lymph emerges nearly as concentrated as plasma. 8 However, increased efferent collecting vessel pressure changed the filtration properties of the LN and ultimately led to markedly leaky afferent lymphatics. 9 Lymphatic collecting vessels are surrounded by fat throughout the body.…”