Endothelial P-selectin and VCAM-1 each can function as primary adhesive mechanisms for T cells under conditions of flow

Konstantinos Konstantopoulos, Sharad Kukreti, C. Wayne Smith, Larry V. McIntire

Research output: Contribution to journalArticlepeer-review

Abstract

This study demonstrates that endothelial P- selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), are capable of supporting extensive primary adhesion of T cells under flow. To address this issue, we used human umbilical vein endothelial cells (HUVECs) stimulated with histamine, interleukin-4 (IL-4), or interferon-γ (IFN-γ) that provide essentially a P-selectin, VCAM-1, or ICAM-1 surface, respectively, in a physiologically relevant cell type. Monoclonal antibody (mAb) blockade studies were carried out to confirm the specificity of these adhesive interactions and rule out a number of other potentially important adhesion molecules. Quantitation of adhesion showed that almost all of the interacting T cells rolled on histamine-stimulated HUVECs or CHO-P cell/monolayers. In contrast, ~ 20% of the total interacting T cells with 24-h IL-4-treated HUVECs were fifmly adherent, mAb blocking experiments revealed that T cell adhesion to IL-4-treated HUVECs is α4-VCAW-1 dependent, Furthermore, mAb 4B9 directed against domain 1 of VCAM-1 eliminated adhesion, suggesting that α4 integrins may not interact with either the alternatively spliced domain 4 of VCAM-1 or fibronectin in this process. At a wall shear stress of 2 dyn/cm2, the mean T cell rolling velocities were significantly lower on 24-h IL-4-activated HUVECs (10.2 ± 2.6 μm/s) compared with either CHO-P cells (15.6 ± 3.1 μm/s) or histamine-stimulated HUVECs (16.6 ± 6.1 μm/s). ICAM-1, expressed on the surface of 24-h IFN-γ-activated HUVECs pretreated with an anti-VCAM-1 mA to eliminate any VCAM-I-dependent contribution, did not support T cell adhesion under shear conditions, Together these data indicate that T cell primary adhesion can be mediated by both endothelial P-selectin and VCAM-1 but not ICAM-1. α4 integrins are highly versatile molecules, capable of initiating T cell rolling interactions and mediating firm arrest on activated endothelium.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalJournal of Leukocyte Biology
Volume61
Issue number2
DOIs
StatePublished - Feb 1997
Externally publishedYes

Keywords

  • Adhesion molecules
  • Cell-to-cell interactions
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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