NEUTROPHIL MIGRATION ACROSS MONOLAYERS OF CYTOKINE-PRESTIMULATED ENDOTHELIAL-CELLS - A ROLE FOR PLATELET-ACTIVATING-FACTOR AND IL-8

被引:190
作者
KUIJPERS, TW [1 ]
HAKKERT, BC [1 ]
HART, MHL [1 ]
ROOS, D [1 ]
机构
[1] UNIV AMSTERDAM,EXPTL & CLIN IMMUNOL LAB,AMSTERDAM,NETHERLANDS
关键词
D O I
10.1083/jcb.117.3.565
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 < 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 formyl-methionyl-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 downmodulated; both WEB 2086 and anti-IL-8 antiserum partially prevented this downmodulation 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.
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页码:565 / 572
页数:8
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