Is lymphatic status related to regression of inflammation in Crohn's disease?

2012

Tonelli F, Giudici F, Liscia G.

Source

Francesco Tonelli, Francesco Giudici, Gadiel Liscia, Department of Clinical Physiopathology, University of Florence, Surgical Unit, 50134 Florence, Italy.

Abstract

AIM:

To investigate the status of the lymphatic vessels in the small bowel affected by Crohn's disease (CD) at the moment of surgery.

METHODS:

During the period January 2011-June 2011, 25 consecutive patients affected by CD were operated on in our Institution. During surgery, Patent Blue V was injected subserosally and the way it spread along the subserosa of the intestinal wall, through the mesenterial layers towards the main lymphatic collectors and eventually to the lymph nodes was observed and recorded. Since some patients had been undergone strictureplasty at previous surgery, we also examined the status of intestinal lymph vessels after previous strictureplasties. The same procedure was performed in a control group of 5 patients affected by colorectal cancer. Length of lesions, caliber, maximal thickness of the diseased intestinal wall, thickness of the wall at injection site and thickness of the mesentery were evaluated at surgery.

RESULTS:

We observed three features after the injection of Patent Blue V in the intestinal loops: (1) Macroscopically healthy terminal ileum of patients with CD or colon cancer showed thin lymphatic vessels linearly directed toward the mesentery; (2) In mild lesions in which the intestinal wall did not reach 8 mm of thickness, we observed short, wide and tortuous lymphatic vessels directed longitudinally along the intestinal axis toward disease-free areas and then transversally toward the mesentery; and (3) Injection in the severely affected lesions, that had a thickness of the intestinal wall over 10 mm, did not show any feature of lymphatic vessels at least on the subserosal surface. There was a correlation between the thickness of the parietal wall and the severity of the lymphatic alterations. Normal lymphatic vessels were observed at previous strictureplasties in the presence of complete regression of the inflammation.

CONCLUSION:

Injection of Patent Blue V in the intestinal wall could help distinguish healthy tracts of the small bowel from those macroscopically borderline.

KEYWORDS:

Crohn’s disease, Inflammation, Intestinal wall, Lymphatic vessels, Mesentery, Patent blue V, Strictureplasty, Surgery, Thickness

WJGS

Lymphatic vessels in health and disease.

Dec 2012

Kesler CT, Liao S, Munn LL, Padera TP.

Source

E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.

Abstract

The lymphatic vasculature plays vital roles in tissue fluid balance, immune defense, metabolism, and cancer metastasis. In adults, lymphatic vessel formation and remodeling occur primarily during inflammation, development of the corpus luteum, wound healing, and tumor growth. Unlike the blood circulation, where unidirectional flow is sustained by the pumping actions of the heart, pumping actions intrinsic to the lymphatic vessels themselves are important drivers of lymphatic flow. This review summarizes critical components that control lymphatic physiology. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1201 For further resources related to this article, please visit the WIREs website.

Wiley OnLine

Corneal angiogenesis and lymphangiogenesis.

Oct 2012

Regenfu B, Bock F, Cursiefen C.

Source

Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.

Abstract

PURPOSE OF REVIEW:

The purpose of the present review is to describe new antilymphangiogenic treatment strategies and recent findings on strain-dependency of corneal lymphangiogenesis and the interdependency between blood and lymphatic vessel growth.

RECENT FINDINGS:

Studies on mice have revealed that apart from haemangiogenesis, lymphangiogenesis can also differ markedly between several mouse strains under normal and inflammatory conditions. Although haemangiogenesis and lymphangiogenesis are closely interconnected in their spatial-temporal patterning, recent data suggest that they can also occur independently.

SUMMARY:

Understanding the coordinated regulation of blood and lymphatic vessel growth and genetic factors determining lymphangiogenesis in more detail could improve the development of specifically targeted antihaemangiogenic or antilymphangiogenic strategies.

Lippincott, Wilkins & Williams

Lymphangiogenesis in development and disease

Lymphangiogenesis in development and disease

Thrombosis and Haemostasis 2007

Ruediger Liersch1, Michael Detmar2
1Department of Medicine, Hematology and Oncology, University Hospital Muenster, Muenster, Germany; 2Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland

Summary

The lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells.The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. They have also identified molecular pathways whose mutation- al inactivation leads to human diseases associated with lymphedema. Moreover, the lymphatic system plays a major role in chronic inflammatory diseases and in transplant rejection. Importantly, malignant tumors can directly promote lymphangiogenesis within the primary tumor and in draining lymph nodes, leading to enhanced cancer metastasis to lymph nodes and beyond. Based upon these findings, novel therapeutic strategies are currently being developed that aim at inhibiting or promoting the formation and function of lymphatic vessels in disease.

Keywords
Lymphatic endothelium, lymphangiogenesis, lymphedema, inflammation, cancer metastasis

Schattauer

The Primary Valves in the Initial Lymphatics during Inflammation.

The Primary Valves in the Initial Lymphatics during Inflammation.

Lymphat Res Biol. 2007
Lynch PM,
Delano FA,
Schmid-Schonbein GW.
Department of Bioengineering, University of California San Diego, La Jolla, California., Supported by United States Public Health Service Grant HL 10881.

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 mum and 0.8 mum 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.

PMID: 17508898 [PubMed - in process]