Eosinophil transendothelial migration induced by cytokines. I. Role of endothelial and eosinophil adhesion molecules in IL-1β-induced transendothelial migration

M. Ebisawa, B. S. Bochner, S. N. Georas, R. P. Schleimer

Research output: Contribution to journalArticlepeer-review

Abstract

IL-1β promotes adhesiveness in human umbilical vein endothelial cells (HuVEC) for eosinophils through expression of adhesion molecules including intercellular adhesion molecules-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). Using an in vitro endothelial monolayer system, we examined whether IL-1β or TNF-α can promote eosinophil transendothelial migration. We also evaluated the contributions of ICAM-1, E-selectin, VCAM- 1, leukocyte adhesion complex (CD11/18), and very late Ag-4 (CD11b/18) (VLA- 4) in this process using blocking mAb, and determined the changes in expression of CD11b and L-selectin on eosinophils that had undergone transmigration. IL-1β and TNF-α treatment of HuVEC (4 h, 5 ng/ml) induced significant transendothelial migration of eosinophils (a 4.1 ± 0.4-fold (IL- 1β) and 2.0 ± 0.9-fold (TNF-α) increase from the spontaneous value of 3.2 ± 0.3%). Increased CD11b expression and shedding of L-selectin were observed on eosinophils following IL-1β-induced eosinophil transendothelial migration. Studies with mAb revealed that blockade of either ICAM-1 or CD11/18 inhibited transmigration, while antibodies against VCAM-1 and VLA-4 had no inhibitory effect. Among antibodies which block β2 integrins, anti- CD18 mAb had the best inhibitory effect (88% inhibition). The combined inhibitory effect of anti-CD11a mAb and anti-CD11b mAb was roughly equal to that of anti-CD18, although anti-CD11a (31% inhibition) and anti-CD11b (52% inhibition) were less effective individually. Anti-ICAM-1 by itself inhibited IL-1β-induced eosinophil transendothelial migration (24% inhibition) whereas neither anti-E-selectin nor anti-VCAM-1 were effective inhibitors. Interestingly, the combination of anti-E-selectin and anti-VCAM-1 with anti- ICAM-1 inhibited IL-1β-induced eosinophil transendothelial migration significantly better (53% inhibition) than anti-ICAM-1 alone. These results suggest that although the initial attachment of eosinophils to IL-1β- activated endothelial cells involves VCAM-1, E-selectin, and ICAM-1, the subsequent transendothelial migration process relies heavily on ICAM-1 and CD11/18. Finally, the changes that eosinophils have been observed to undergo during infiltration in vivo, namely increased expression of CD11/18 and shedding of L-selectin, appear to take place as a direct result of the interaction between eosinophils and endothelial cells.

Original languageEnglish (US)
Pages (from-to)4021-4028
Number of pages8
JournalJournal of Immunology
Volume149
Issue number12
StatePublished - 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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