Interleukin-8 induces neutrophil transendothelial migration.
Interleukin-8 (IL-8) is a potent neutrophil chemotactic stimulant. We have used chemically synthesized IL-8 to investigate its role in human neutrophil adhesion and transendothelial migration. IL-8 enhanced the adhesiveness of human neutrophils to plastic, and to both unstimulated and tumour necrosis factor (TNF)-stimulated endothelial monolayers in vitro. Using a two-compartment model separated by a confluent endothelial monolayer, we have shown that IL-8 chemotactic stimulation induced transmigration across the monolayer of up to 87.4 +/- 2.1% of added neutrophils (compared to random unstimulated transmigration of 2.2 +/- 0.7%), while chemokinetic stimulation led to transmigration of 21 +/- 3.8% of neutrophils. Preincubation of endothelium with TNF also induced transmigration in this model, and was additive when combined with an IL-8 chemotactic stimulus. Endothelial permeability was increased at maximal rates of chemotactic transmigration, which may correlate with increased permeability of vessels at inflammatory sites in vivo. The property of IL-8 to stimulate movement of neutrophils across endothelial monolayers in vitro supports the concept of a central role for this molecule in the accumulation of neutrophils at inflammatory lesions in vivo.
Smith
W B
WB
Division of Human Immunology, Institute of Medical and Veterinary Sciences, Adelaide, South Australia.
Gamble
J R
JR
Clark-Lewis
I
I
Vadas
M A
MA
D002199:Capillary Permeability; D002448:Cell Adhesion; D002465:Cell Movement; D002630:Chemotactic Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011137:Polystyrenes; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014471:Umbilical Veins / Q000378:metabolism
D002630:Chemotactic Factors; D016209:Interleukin-8; D011137:Polystyrenes; D014409:Tumor Necrosis Factor-alpha