Related Experiment Videos
Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease
M Saharay1, D A Shields, J B Porter
1Department of Surgery, University College London Medical School, United Kingdom.
Insights
Venous hypertension causes leukocyte adhesion to leg microcirculation endothelium in chronic venous disease patients. These activated leukocytes, including neutrophils and monocytes, remain sequestered, contributing to lipodermatosclerosis and ulceration.
Area of Science:
- Vascular Biology
- Dermatology
- Immunology
Background:
- Chronic venous disease (CVD) is linked to leukocyte trapping and activation in leg skin microcirculation, potentially causing lipodermatosclerosis and ulceration.
- Ambulatory venous hypertension is a recognized physiological factor contributing to ulceration in CVD.
- Investigating leukocyte-endothelial interactions under venous hypertension is crucial for understanding CVD pathogenesis.
Purpose of the Study:
- To investigate leukocyte endothelial adhesion in patients with chronic venous disease subjected to short-term venous hypertension.
- To determine if leukocyte activation and adhesion patterns differ between patients with and without skin changes associated with venous disease.
Main Methods:
- Studied two groups of patients with venous disease: 15 with varicose veins and skin changes, and 15 with varicose veins but no skin changes.
- Measured leukocyte surface CD11b and L-selectin (CD62L) expression via flow cytometry before, during, and after a 30-minute venous hypertension period induced by standing.
- Quantified plasma-soluble L-selectin levels using ELISA to assess leukocyte-endothelial adhesion.
Main Results:
- In patients with skin changes, neutrophil CD11b levels decreased during venous hypertension, while monocyte CD11b levels decreased during and after hypertension.
- Neutrophil and monocyte L-selectin levels decreased with venous hypertension and remained low afterward in both groups.
- Plasma-soluble L-selectin increased in both groups during venous hypertension, indicating leukocyte adhesion to the endothelium, with similar rises observed in patients with and without skin changes.
Conclusions:
- Short-term venous hypertension leads to the sequestration of activated neutrophils and monocytes within the leg microcirculation of patients with venous disease.
- These leukocytes adhere to the endothelium, release L-selectin, and remain trapped in the limb even after venous pressure normalization.
- The observed leukocyte sequestration patterns do not significantly differ between patients with uncomplicated varicose veins and those with associated skin changes.
Purpose:
It has been suggested that leukocyte trapping and activation in the microcirculation of the leg skin causes lipodermatosclerosis and ulceration in patients with chronic venous disease. Ambulatory venous hypertension is accepted as the physiologic factor that leads to ulceration. We investigated leukocyte endothelial adhesion in patients who were subjected to short-term venous hypertension.
Methods:
Two groups of patients with venous disease were studied: group 1, varicose veins with skin changes (n = 15); and group 2, varicose veins without skin changes (n = 15). Blood samples were taken from a foot vein before and after standing for 30 minutes to raise the venous pressure in the lower limb, and after lying supine again for 10 minutes. The samples were analyzed for leukocyte surface CD11b and L-selectin (CD62L) expression using a flow cytometer. Plasma-soluble L-selectin was also measured using an enzyme-linked immunosorbent assay.
Results:
In patients with skin changes, median neutrophil CD11b levels fell from 4.66 to 3.83 arbitrary units (p = 0.005, Wilcoxon) after 30 minutes of venous hypertension, Median monocyte CD11b levels fell from 7.65 to 5.8 arbitrary units (p = NS, Wilcoxon) after venous hypertension and then fell further to 5.43 arbitrary units (p = 0.02 vs baseline; Wilcoxon) when the venous hypertension was removed. Neutrophil and monocyte L-selectin levels also fell in response to venous hypertension, remaining low even after venous hypertension was removed. A similar pattern was seen in patients with uncomplicated varicose veins. There was a rise in soluble L-selectin in the plasma of both groups of patients after venous hypertension, reflecting leukocyte adhesion to endothelium. In the group of patients with skin changes the level of soluble L-selectin rose from 695 ng/ml to 836 ng/ml (p = 0.02, Wilcoxon), and in the group without skin changes the rise was from 700 ng/ml to 801 ng/ml (p = 0.02, Wilcoxon).
Conclusion:
Venous hypertension results in sequestration of the more activated population of neutrophils and monocytes in the microcirculation of the leg in patients with venous disease. These cells bind to the endothelium, releasing L-selectin, and do not emerge from the limb when venous hypertension is reversed. These findings do not differ between patients with varicose veins and those with skin changes.