IL-8 induces a transient arrest of rolling eosinophils on human endothelial cells.
Eosinophils exhibit a rolling interaction with E-selectin-expressing endothelium, and need to be activated by inflammatory mediators to firmly adhere to this surface. This study shows that IL-8 induces a transient arrest of unprimed eosinophils that roll on E-selectin present on TNF-alpha-activated HUVEC in an in vitro flow chamber. This process was antagonized by neutralizing Abs directed against IL-8 showing the specificity of the IL-8 effect. Furthermore, blocking Abs against both alpha(4) and beta(2) integrins inhibited the IL-8-induced transient arrest while these Abs had no effect when they were added separately. The IL-8-induced arrest was pertussis toxin sensitive. Studying the effect of IL-8 in more detail, we evaluated putative changes in intracellular Ca(2+) concentration in eosinophils induced by IL-8. We could show that IL-8 induces a transient rise in intracellular Ca(2+) concentration in approximately 40% of the cells provided that the eosinophils are interacting with endothelial cells or fibronectin-coated surfaces. Together these data show that resting eosinophils respond to IL-8 provided that the cells adhere on physiological surfaces. The induction of a transient arrest provides a new level of chemokine-induced regulation of leukocyte adhesion under flow conditions.
Ulfman
L H
LH
Department of Pulmonary Diseases and Haematology, University Medical Center, Utrecht, The Netherlands.
Joosten
D P
DP
van der Linden
J A
JA
Lammers
J W
JW
Zwaginga
J J
JJ
Koenderman
L
L
D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D002469:Cell Separation; D015194:Diffusion Chambers, Culture; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism; D012212:Rheology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D005353:Fibronectins; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium