Neutrophil migration across monolayers of cytokine-prestimulated endothelial cells: a role for platelet-activating factor and IL-8.
In a previous study we observed that neutrophils respond with a rapid rise in [Ca2+]i during adherence to cytokine-activated endothelial cells (EC), caused by EC membrane-associated platelet-activating factor (PAF). In the present study, we investigated whether this form of PAF was important in neutrophil adherence and migration across monolayers of rIL-1 beta- or rTNF alpha-prestimulated EC. PAF receptor antagonists prevented neutrophil migration across cytokine-pretreated EC by approximately 60% (P less than 0.005) without interfering with the process of adherence. The antagonists WEB 2086 and L-652,731 had no effect on neutrophil migration across resting EC induced by formylmethionyl-leucyl-phenylalanine (FMLP). A murine anti-IL-8 antiserum was found to also partially inhibit the neutrophil transmigration across cytokine-activated EC. When the anti-IL-8 antiserum was used in combination with a PAF receptor antagonist, neutrophil migration across cytokine-pretreated monolayers of EC was completely prevented. During transmigration, LAM-1 and CD44 on the neutrophils were down-modulated; both WEB 2086 and anti-IL-8 antiserum partially prevented this down-modulation caused by cytokine-prestimulated EC. Our results indicate that human neutrophils are activated and guided by EC-associated PAF and EC-derived IL-8 during the in vitro diapedesis in between cytokine-stimulated EC.
Kuijpers
T W
TW
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Hakkert
B C
BC
Hart
M H
MH
Roos
D
D
D000954:Antigens, Surface / Q000096:biosynthesis; D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D005260:Female; D005663:Furans / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D013268:Stimulation, Chemical; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D000954:Antigens, Surface; D001381:Azepines; D005663:Furans; D016209:Interleukin-8; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; C052518:WEB 2086; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran