Transmural flow modulates cell and fluid transport functions of lymphatic endothelium

Dimana O. Miteva, Joseph M. Rutkowski, J. Brandon Dixon, Witold Kilarski, Jacqueline D. Shields, Melody A. Swartz

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Rationale: Lymphatic transport of peripheral interstitial fluid and dendritic cells (DCs) is important for both adaptive immunity and maintenance of tolerance to self-antigens. Lymphatic drainage can change rapidly and dramatically on tissue injury or inflammation, and therefore increased fluid flow may serve as an important early cue for inflammation; however, the effects of transmural flow on lymphatic function are unknown. Objective: Here we tested the hypothesis that lymph drainage regulates the fluid and cell transport functions of lymphatic endothelium. Methods and Results: Using in vitro and in vivo models, we demonstrated that lymphatic endothelium is sensitive to low levels of transmural flow. Basal-to-luminal flow (0.1 and 1 μm/sec) increased lymphatic permeability, dextran transport, and aquaporin-2 expression, as well as DC transmigration into lymphatics. The latter was associated with increased lymphatic expression of the DC homing chemokine CCL21 and the adhesion molecules intercellular adhesion molecule-1 and E-selectin. In addition, transmural flow induced delocalization and downregulation of vascular endothelial cadherin and PECAM-1 (platelet/endothelial cell adhesion molecule-1). Flow-enhanced DC transmigration could be reversed by blocking CCR7, intercellular adhesion molecule-1, or E-selectin. In an experimental model of lymphedema, where lymphatic drainage is greatly reduced or absent, lymphatic endothelial expression of CCL21 was nearly absent. Conclusions: These findings introduce transmural flow as an important regulator of lymphatic endothelial function and suggest 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.

Original languageEnglish (US)
Pages (from-to)920-931
Number of pages12
JournalCirculation Research
Volume106
Issue number5
DOIs
StatePublished - Mar 19 2010

Fingerprint

Lymphatic Endothelium
Dendritic Cells
Drainage
E-Selectin
Intercellular Adhesion Molecule-1
Chemokine CCL21
Aquaporin 2
CD31 Antigens
Inflammation
Lymphedema
Extracellular Fluid
Autoantigens
Adaptive Immunity
Lymph
Dextrans
Cues
Permeability
Theoretical Models
Down-Regulation
Lymph Nodes

Keywords

  • CCL21
  • ICAM-1
  • In vitro
  • Inflammation
  • Lymphedema
  • Overhydration

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Miteva, D. O., Rutkowski, J. M., Dixon, J. B., Kilarski, W., Shields, J. D., & Swartz, M. A. (2010). Transmural flow modulates cell and fluid transport functions of lymphatic endothelium. Circulation Research, 106(5), 920-931. https://doi.org/10.1161/CIRCRESAHA.109.207274

Transmural flow modulates cell and fluid transport functions of lymphatic endothelium. / Miteva, Dimana O.; Rutkowski, Joseph M.; Dixon, J. Brandon; Kilarski, Witold; Shields, Jacqueline D.; Swartz, Melody A.

In: Circulation Research, Vol. 106, No. 5, 19.03.2010, p. 920-931.

Research output: Contribution to journalArticle

Miteva, DO, Rutkowski, JM, Dixon, JB, Kilarski, W, Shields, JD & Swartz, MA 2010, 'Transmural flow modulates cell and fluid transport functions of lymphatic endothelium', Circulation Research, vol. 106, no. 5, pp. 920-931. https://doi.org/10.1161/CIRCRESAHA.109.207274
Miteva DO, Rutkowski JM, Dixon JB, Kilarski W, Shields JD, Swartz MA. Transmural flow modulates cell and fluid transport functions of lymphatic endothelium. Circulation Research. 2010 Mar 19;106(5):920-931. https://doi.org/10.1161/CIRCRESAHA.109.207274
Miteva, Dimana O. ; Rutkowski, Joseph M. ; Dixon, J. Brandon ; Kilarski, Witold ; Shields, Jacqueline D. ; Swartz, Melody A. / Transmural flow modulates cell and fluid transport functions of lymphatic endothelium. In: Circulation Research. 2010 ; Vol. 106, No. 5. pp. 920-931.
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