Inappropriate neutrophil activation in venous disease

Abstract

Neutrophil oxygen radical production was studied in 18 limbs with class 2 or 3 venous disease and compared with that of nine normal limbs. Neutrophils were isolated from arm and leg venous samples. Free radical production was determined using chemiluminescence after stimulation with the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) or the ester phorbol myristate acetate (PMA). The ratio of leg to arm luminescence was greater after FMLP stimulation in patients with venous disease (median 1.52 (95 per cent confidence interval (c.i.) 1.27-2.60)) than in controls (median 0.97 (95 per cent c.i. 0.70-1.12); P < 0.01). These changes were not observed with PMA (venous disease 1.16 (95 per cent c.i. 1.05-1.40); controls 0.95 (95 per cent c.i. 0.78-1.24)). There were fewer FMLP receptors on activated leg neutrophils (median 20.19 (95 per cent c.i. 3.58-51.42) fluorescence units) than arm neutrophils (median 36.03 (95 per cent c.i. 13.00-65.28) fluorescence units; P < 0.05), indicating an amplification of signal transduction. Intracellular calcium imaging demonstrated a larger release of calcium after stimulation of leg neutrophils (median 25.0 per cent (95 per cent c.i. 15.7-43.9 per cent)) compared with neutrophils from the arm (median 8.0 per cent (95 per cent c.i. 5.6-16.1 per cent); P = 0.04), demonstrating calcium-dependent activation. Neutrophils in patients with chronic venous disease inappropriately produce more oxygen free radical as a result of amplification of a calcium-dependent signal pathway.

Postischemic Leukocyte/Endothelial Cell Interactions and Microvascular Barrier Dysfunction in Skeletal Muscle: Cellular Mechanisms and Effect of Daflon® 500 mg

“…The development of postisch emic edema may be further enhanced during l/R by an elevation in capillary pressure induced by the increase in venous resistance that may arise secondary to partial lumenal occlusion of postcapillary venules by leukocytes adhering to the wall of these vessels. For tissues that can not readily expand to accomodate increased interstitial fluid volume such as the brain, kidneys, and compartmented muscle, the accumulation of excessive interstitial ln tJ Microcirc 1997;17(suppl 1):11-17 13 fluid can increase interstitial fluid pressure to a level suffi cient to cause extravascular compression of capillaries and thus the development of no-reflow. Several lines of evidence support this hypothesis for the development of leukocyte-dependent capillary no reflow in skeletal muscle.…”

Pathophysiology of Venous Leg Ulceration

“…Activated white cells and endothelium are also a potential source of platelet-activating factors. Free radical produc tion by activated white cells in patients with venous dis ease of the legs has now been confirmed and shown to be the result of amplification of a calcium-dependent signal pathway [17,18]. Strong experimental evidence support ing the central role of white cell endothelial interaction in venous ulceration comes from the recent evidence, in a hamster model, that blockade of this interaction attenu ates the typical capillary changes observed in chronic venous insufficiency [ 19].…”

Venous Hypoxia: A Poorly Studied Etiological Factor of Varicose Veins

“…Moreover, leucocytes in the blood of varicose veins demonstrated increased oxidative stress compared with arm veins in patients with CVI [38,39]. Leucocyte trapping and oxygen free radical (superoxide dismutase and superoxide anions) retention in lower limbs were also significantly increased in patients with varicose veins compared to those without in gravity-dependent positions [40].…”