Publications & Reports

Lymphocyte-facilitated tumour cell adhesion to endothelial cells: the role of high affinity leucocyte integrins.

Neeson PJ, Thurlow PJ, Jamieson GP, Bradley C
Immunology Unit, Division of Laboratory Medicine, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia. pneeson@mail.med.upenn.edu

Abstract

AIM: Lymphocytes transiently express an active form of the beta_2 integrin LFA-1 (LFA-1Af) which has conformational changes in extracellular domains enabling higher affinity binding to the ligand ICAM-1. In this study, we investigated the role of lymphocytes bearing LFA-1Af as potential mediators of binding of ICAM-1-positive tumour cells to endothelium. METHODS: LFA-1 expression on 51Cr-PBLs was modulated in order to express high affinity LFA-1Af and conjugates were formed with 35S-labelled COLO526. The binding of the conjugates to resting or IL-1beta-stimulated human umbilical vein endothelial cells (HUVECs) was then assessed via a modified radioactive HUVEC binding assay. In addition, the binding of PBL-COLO526 conjugates to HUVECs was demonstrated by confocal microscopy. RESULTS: The binding of COLO526 to endothelial cells did not change significantly between unstimulated and stimulated HUVECs. In addition, pre-incubating the COLO526 with fresh PBLs did not significantly alter the binding of COLO526 to resting or activated HUVECs; whereas, in the presence of PBLs with LFA-1Af, the COLO526 conjugate binding dramatically increased from basal levels to 41% on resting HUVECs and 81% on stimulated HUVECs. COLO526-PBL(LFA-1Af) conjugate adhesion to stimulated HUVECs was inhibited by blocking antibody to LFA-1 (50%), VLA-4 (32%) or L-selectin (40%). Antibodies to the HUVEC adhesion molecules ICAM-1, VCAM-1 and E-selectin also inhibited COLO526-PBL(LFA-1Af) conjugate binding to activated HUVECs by 79, 60 and 73%, respectively. CONCLUSIONS: PBLs bearing LFA-1Af can enhance COLO526 adhesion to both resting and activated HUVECs. Furthermore, blocking studies demonstrate that a range of pathways are involved in this phenomenon (LFA-1/ICAM-1, VLA4/VCAM-1, L-selectin/E-selectin). These studies have identified a novel alternative pathway for lymphocyte-facilitated tumour cell adhesion to endothelial cells.

Publication

  • Journal: Pathology
  • Published: 01/02/2003
  • Volume: 35
  • Issue: 1
  • Pagination: 50-55

Author