Interleukin-8 increases endothelial permeability independent of neutrophils.
Interleukin-8 (IL-8) has been associated with a variety of hyperinflammatory states and adverse clinical events. Circulating IL-8 levels correlate with the severity of tissue trauma, and excessive elevations of IL-8 are associated with postinjury adult respiratory distress syndrome and multiple organ failure. While IL-8 is a potent neutrophil (PMN) chemoattractant and activator and enhances PMN transendothelial migration, it also acts to inhibit PMN adhesion to stimulated endothelial cells (ECs). We hypothesized that IL-8 could interact directly with ECs to increase permeability independent of PMNs. Human umbilical vein ECs (HUVECs) were cultured on collagen-coated micropore filters, and integrity of the EC monolayer measured by albumin flux across the filter. Cytochalasin D was used as a positive control. IL-8 induced increased permeability at a concentration of 1000 ng/mL. This effect was abrogated by preincubation of HUVECs with a protein synthesis inhibitor (cycloheximide). These data suggest a role for IL-8 in promoting endothelial leak independent of PMNs, via a mechanism involving protein synthesis.
Biffl
W L
WL
Department of Surgery, Denver General Hospital, CO 80204-4507, USA.
Moore
E E
EE
Moore
F A
FA
Carl
V S
VS
Franciose
R J
RJ
Banerjee
A
A
D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D014471:Umbilical Veins / Q000187:drug effects
D016209:Interleukin-8; D015638:Cytochalasin D