Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer.

  title={Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer.},
  author={Helge Wiig and Melody A. Swartz},
  journal={Physiological reviews},
  volume={92 3},
The interstitium describes the fluid, proteins, solutes, and the extracellular matrix (ECM) that comprise the cellular microenvironment in tissues. Its alterations are fundamental to changes in cell function in inflammation, pathogenesis, and cancer. Interstitial fluid (IF) is created by transcapillary filtration and cleared by lymphatic vessels. Herein we discuss the biophysical, biomechanical, and functional implications of IF in normal and pathological tissue states from both fluid balance… 

Tumor Interstitial Fluid Formation, Characterization, and Clinical Implications

The present review discusses available techniques for TIF isolation, results from subsequent characterization and implications of recent findings with respect to fluid filtration and uptake of macromolecular therapeutic agents.

On-chip engineered human lymphatic microvasculature for physio-/pathological transport phenomena studies

A microfluidic-based approach is developed that allows for precise control over the transport of growth factors and interstitial fluid flow, which is leverage to recapitulate the in vivo growth of lymphatic capillaries and is validated by characterizing the drainage rate of extracellular solutes and proteins.

Interstitial fluid lipoproteins

Study of the concentration, composition, functionality, and turnover of interstitial fluid lipoproteins will be of great future interest for understanding how tissue cholesterol metabolism is regulated, and how different diseases link to increased risk for development of atherosclerosis.

Anatomy and roles of lymphatics in inflammatory diseases

Lymphatic structure function within the gut, heart and central nervous system is reviewed, discussing potential roles of these lymphatics in the etiology of inflammatory bowel disease, myocarditis and neurovascular disease, and as novel targets for therapeutic management of several disease states.

Lymphatic Vessels and Their Surroundings: How Local Physical Factors Affect Lymph Flow

How known physical stimuli affect intrinsic contractility and thus lymph flow is focused on and the most likely cellular mechanisms that mediate this phenomenon are described.

How to Cross the Lymphatic Fence: Lessons From Solute Transport.

It is reported that transcellular and paracellular pathways are equally important for lymphatic solute transport and that both transports contribute to the increased lymphatic permeability on a rise in transmural flow and in case of inflammation.

Lymphangiogenesis Facilitates Initial Lymph Formation and Enhances the Dendritic Cell Mobilizing Chemokine CCL21 Without Affecting Migration

An expanded lymphatic network is capable of enhanced chemoattractant production, and lymphangiogenesis will facilitate initial lymph formation favoring increased clearance of fluid in situations of augmented fluid filtration.

Radiation-induced changes in microcirculation and interstitial fluid pressure affecting the delivery of macromolecules and nanotherapeutics to tumors

It is concluded that modulations in vascular, transvascular, and interstitial transport by irradiation of solid tumors are rather unclear so far and translation of experimental data into the clinical setting thus needs to be undertaken with especial care.

Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress

Findings reveal the importance of intracellular transport in steady-state lymph formation and suggest that LECs use transcellular mechanisms in parallel to the well-described paracellular route to modulate solute transport from the interstitium according to biomechanical cues.



Capillary Fluid Exchange: Regulation, Functions, and Pathology

Transcapillary fluid filtration allows for continuous turnover of water bathing tissue cells, providing the medium for diffusional flux of oxygen and nutrients required for cellular metabolism and removal of metabolic byproducts.

Interstitial Flow as a Guide for Lymphangiogenesis

The data suggest that interstitial fluid channeling precedes and may even direct lymphangiogenesis (in contrast to blood angiogenesis, in which fluid flow proceeds only after the vessel develops); thus, a novel and robust model is introduced for correlating molecular events with functionality in lymphang iogenesis.

The Role of Interstitial Stress in Lymphatic Function and Lymphangiogenesis

The working hypothesis is that the physiological driving force for lymphangiogenesis is the need for organized interstitial fluid flow, and the rationale and background for such an approach are outlined.

Interstitial fluid: the overlooked component of the tumor microenvironment?

The emergence of sensitive proteomic technologies has made the interstitial fluid compartment in general and that of tumors in particular a highly valuable source for tissue-specific proteins that may serve as biomarker candidates.

Transmural Flow Modulates Cell and Fluid Transport Functions of Lymphatic Endothelium

Transmural flow is introduced as an important regulator of lymphatic endothelial function and suggested that flow might serve as an early inflammatory signal for lymphatics, causing them to regulate transport functions to facilitate the delivery of soluble antigens and DCs to lymph nodes.

Transport of molecules in the tumor interstitium: a review.

  • R. Jain
  • Materials Science
    Cancer research
  • 1987
High interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells in the tumor interstitium, especially in large tumors.

Molecular Regulation of Lymphatic Contractility

This chapter reviews the understanding of the important molecular mechanisms, the calcium regulation, and the contractile/regulatory proteins that control lymphatic contractions that are thought to occur via regulation of lymphatic muscle contractions.

Transcapillary exchange: role and importance of the interstitial fluid pressure and the extracellular matrix.

This review will summarize current knowledge on the role of the extracellular matrix (ECM) in general and on the interstitial fluid pressure (P(if)) in particular with regard to their importance in

Lymphatic endothelial cells, lymphangiogenesis, and extracellular matrix.

  • R. Ji
  • Biology
    Lymphatic research and biology
  • 2006
Growing recognition of the multiple functions of ECM and LEC molecules for important physiological and pathological events may be helpful in identifying the crucial changes in tissues subjected to lymph circulation and ultimately in the search for rational therapeutic approaches to prevent lymphatic-associated disorders.

Regulatory mechanisms in lymphatic vessel contraction under normal and inflammatory conditions.