Expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin and their ligands VLA-4 and LFA-1 in chronic venous leg ulcers

Weyl, A; Vanscheidt, Wolfgang; Weiss, Johannes M.; Peschen, M.; Schöpf, Erwin; Simon, Jan C.

doi:10.1016/s0190-9622(96)90432-6

Cited by 56 publications

(43 citation statements)

References 37 publications

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“…Endothelial leucocyte adhesion molecule-1 (ELAM-1) may be slightly upregulated, but vascular cellular adhesion molecule (VCAM) appears to be normal in patients without venous ulceration. In skin taken from regions adjacent to leg ulcers, upregulated endothelial expression of ICAM-1 and VCAM has been observed without increased amounts of E-selectin [29]. Perturbed endothelium is more likely to attract the adhesion of leucocytes.…”

Section: Histological Studiesmentioning

confidence: 99%

Neutrophil Activation and Mediators of Inflammation in Chronic Venous Insufficiency

Smith¹

1999

J Vasc Res

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The effect of venous hypertension on the state of activation of leucocytes has been investigated in patients with venous disease and control subjects. Leucocytes become ‘trapped’ in the circulation of the leg during periods of venous hypertension produced by sitting or standing. This is greater in the limbs of patients with chronic venous disease than controls. Studies of the plasma levels of neutrophil granule enzymes show that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligand CD11b shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the vascular (VCAM), intercellular (ICAM) and endothelial leucocyte (ELAM) adhesion molecules show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 min of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. I believe that this may be the mechanism that initiates the pathological processes which lead to venous ulceration. It has recently been shown that the venotonic drug Daflon 500 mg (450 mg diosmin, 50 mg hesperidin, Servier, France) influences these processes. Surface expression of CD62L is reduced in neutrophils and monocytes, and plasma levels of soluble endothelial adhesion molecules are reduced. These observations may explain the anti-inflammatory effects of Daflon 500 mg.

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Section: Histological Studiesmentioning

confidence: 99%

Neutrophil Activation and Mediators of Inflammation in Chronic Venous Insufficiency

Smith¹

1999

J Vasc Res

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“…However, to our knowledge, neither the role of macrophages in perpetuating chronic inflammation nor the microenvironmental cues in CVUs that may lead to persistent monocyte/macrophage activation have been addressed in sufficient detail. So far, there is evidence that venous hypertension - caused by venous valve incompetence - results in venous stasis of the lower extremity, low or absent shear stress, and hypoxia, which all trigger endothelial cell activation with "trapping" of monocytes/macrophages and other leukocytes in the microcirculation (13)(14)(15). Activated monocytes/macrophages and other leukocytes transmigrate into the tissue and release high amounts of proinflammatory cytokines (16), proteases (17), and ROS (18,19), which are responsible for the breakdown of the connective tissue and of essential growth factors (20)(21)(22), eventually leading to ulcer formation (1, 2, 9).…”

Section: Introductionmentioning

confidence: 99%

An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice

Sindrilaru¹,

Peters²,

Wieschalka³

et al. 2011

J. Clin. Invest.

952

790

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Uncontrolled macrophage activation is now considered to be a critical event in the pathogenesis of chronic inflammatory diseases such as atherosclerosis, multiple sclerosis, and chronic venous leg ulcers. However, it is still unclear which environmental cues induce persistent activation of macrophages in vivo and how macrophage-derived effector molecules maintain chronic inflammation and affect resident fibroblasts essential for tissue homeostasis and repair. We used a complementary approach studying human subjects with chronic venous leg ulcers, a model disease for macrophage-driven chronic inflammation, while establishing a mouse model closely reflecting its pathogenesis. Here, we have shown that iron overloading of macrophages -as was found to occur in human chronic venous leg ulcers and the mouse model -induced a macrophage population in situ with an unrestrained proinflammatory M1 activation state. Via enhanced TNF-α and hydroxyl radical release, this macrophage population perpetuated inflammation and induced a p16 INK4a -dependent senescence program in resident fibroblasts, eventually leading to impaired wound healing. This study provides insight into the role of what we believe to be a previously undescribed iron-induced macrophage population in vivo. Targeting this population may hold promise for the development of novel therapies for chronic inflammatory diseases such as chronic venous leg ulcers.

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“…However, a later study with wound fluid analysis supported the hypothesis, showing increased levels of inflammation and hypoxia in the microenvironment of the venous ulcer (Trengove et al, 1996). Two studies also showed increased levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in chronic venous insufficiency patients, suggesting increased potential for leukocyte-endothelial adhesion (Weyl et al, 1996;Saharay et al, 1998). Saharay et al (1997) later found that, after 30 minutes of venous hypertension, patients with chronic venous disease exhibited decreased levels of neutrophil CD11b and L-selectin and increased plasma levels of soluble L-selectin.…”

Section: ''Fibrin Cuff'' Theorymentioning

confidence: 93%

“…Duplex ultrasound, the gold standard in diagnosing venous reflux, was used in only half of the studies. Finally, of the 18 observational or interventional studies, 15 did not exclude patients with diabetes (Burnand et al, 1982a, b;Coleridge Smith et al, 1988;Thomas et al, 1988;Cheatle et al, 1990;Trengove et al, 1996;Weyl et al, 1996;Loots et al, 1998;Takase et al, 1999;Danielsson et al, 2003) or infection (Burnand et al, 1982a, b;Coleridge Smith et al, 1988;Thomas et al, 1988;Layton et al, 1994;Trengove et al, 1996;Weyl et al, 1996;Loots et al, 1998;Takase et al, 1999;Abd-El-Aleem et al, 2005). Given the effects of diabetes and infection on chronic inflammation, it is difficult to clearly identify the role of inflammatory cells in chronic venous disease.…”

Section: Inflammatory Cell ''Trap'' Theorymentioning

confidence: 99%

Does Inflammation Have a Role in the Pathogenesis of Venous Ulcers?: A Critical Review of the Evidence

Liu

Margolis

Isseroff

2011

Journal of Investigative Dermatology

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Chronic venous disease, a disorder involving venous return from the legs, is a growing epidemic in the developed world. Numerous studies have been conducted in the past two decades in an attempt to elucidate its underlying pathophysiology. Many theories have been proposed to address the profound inflammatory dysregulation, with the majority focusing on fibrin trap, inflammatory trap, cytokines, growth factors, and matrix metalloproteinases. Although many of these theories have obtained great momentum, much of the data are contradictory. Moreover, many treatments built on these theories have claimed overwhelming success despite insufficient evidence. At the same time, there are few reviews that critically analyze and evaluate these data. Therefore, in this paper, we will provide summaries of the background data and evolution of these theories and examine their supporting evidence.

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Expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin and their ligands VLA-4 and LFA-1 in chronic venous leg ulcers

Cited by 56 publications

References 37 publications

Neutrophil Activation and Mediators of Inflammation in Chronic Venous Insufficiency

Neutrophil Activation and Mediators of Inflammation in Chronic Venous Insufficiency

An unrestrained proinflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice

Does Inflammation Have a Role in the Pathogenesis of Venous Ulcers?: A Critical Review of the Evidence

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