Effects of thalidomide on neutrophil respiratory burst, chemotaxis, and transmigration of cytokine- and endotoxin-activated endothelium

Abstract

Vascular endothelium activated by endotoxin and cytokines plays an important role in organ inflammation and blood leukocyte recruitment. Neutrophils, which are a homogeneous population of effector cells, are rapidly attracted in large numbers to sites of inflammation where they form an early response to infection or injury. Excessive production of various interleukins, TNF, arachidonic acid metabolites, and other substances by neutrophils and macrophages results in systemic endothelial cell injury, a fundamental problem. In the present study, we investigated in vitro the effects of thalidomide (THD) on activation of endothelial cells for enhanced transmigration of neutrophils by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF), and interleukin-1 (IL-1). Modulation of endotoxin- and cytokine-induced neutrophil chemotaxis and respiratory burst by THD were also studied. Treatment of HUVEC with THD in combination with LPS, TNF, and IL-1, respectively, antagonized LPS-activated transmigration of neutrophils but stimulated the effects of TNF and IL-1. All of the agents used-THD, LPS, TNF, and IL-1-inhibited neutrophil chemotaxis. Addition of THD to the neutrophils had no effect on LPS-inhibited chemotaxis whereas the TNF- and IL-1-induced chemotaxis was modulated in a bimodal manner. However, THD failed to influence neutrophil respiratory burst activity. Results demonstrate that THD differentially affects mediator-induced activation of HUVEC and neutrophils.

Syndecan-4 as Antithrombin Receptor of Human Neutrophils

“…Neutrophils were prepared from forearm venous blood of healthy volunteers, anticoagulated with 1.6 mg EDTA/mL of blood. Neutrophil preparation by dextran sedimentation and hypotonic lysis of contaminating erythrocytes using sodium chloride solutions was performed as described previously (10).…”

Thalidomide Inhibits Granulocyte Responses in Healthy Humans after Ex Vivo Stimulation with Bacterial Antigens

“…Treatment of human umbilical vein endothelial cells with thalidomide resulted in stimulation or inhibition of transmigration of neutrophils, depending on the stimulus used (3). Thalidomide attenuated neutrophil chemotaxis in vitro but did not influence respiratory burst activity (3). In the present study we determined whether an oral dose of thalidomide influenced the ability of bacterial antigens to induce granulocyte activation in healthy humans.…”

ACUTE EFFECTS OF TUMOR NECROSIS FACTOR-a ON TESTICULAR GERM CELL APOPTOSIS AND VASCULAR NEUTROPHIL ADHESION IN RATS

“…TNF-a is a natural stimulant of neutrophils which promotes adherence to endothelial cells, migration across endothelial cells and chemotaxis [2,5]. On endothelial cell lines, TNF-a produces a significant increase in intercellular adhesion molecule-1 expression and neutrophil transendothelial passage [15].…”