Very late antigen-4/vascular cell adhesion molecule-1 (VLA-4/VCAM-1) pathway is involved in the transendothelial migration of Lymphocytes in Bancroftian Filariasis

Academic Article

Abstract

  • The role of endothelial vascular cell adhesion molecule-1 (VCAM-1) in the trafficking of lymphocytes from the vascular circulation through endothelium and into sites of filarial inflammation was investigated in asymptomatic microfilaremic (MF; n = 16) and in patients with filaria-associated lymphatic pathology (LP; n = 23). When compared, by human umbilical vein endothelial cell ELISA, with PBMC supernatants generated from MF patients, filarial Ag (Brugia malayi adult Ag (BmA))-stimulated supernatants from LP patients stimulated over 50% more VCAM-1 (lymphatic pathology (LP) = 0.377 relative ELISA units vs MF = 0.246; p = 0.02). No difference was seen between patient groups with nonfilarial Ag (streptolysin O)-stimulated supernatant (LP = 0.160 relative ELISA units vs MF = 0.166). BmA-stimulated supernatants from LP patients stimulated significantly more T cell migration (percentage of relative migration LP = 79.9% vs MF = 25.8%; p = 0.01) through tightly confluent human umbilical vein endothelial cell monolayers cultured on collagen gels. Anti-VCAM-1 inhibited the increased T cell migration induced by BmA-stimulated supernatants by 97.7%, anti-VLA-4 by 74.7%, and blockade of NF-κB-dependent VCAM-1 transcription with 50 μM pyrrolidine dithiocarbamate resulted in 87.7% inhibition. Biopsies from 87.5% of the LP patients, but only 38.5% of the MF patients, demonstrated VCAM-1 on vascular endothelium. BmA-stimulated supernatants pretreated with anti-IL-1 alone resulted in VCAM-1 expression that was 23.7% of that with untreated supernatants while anti-IL-4, anti-IFN-γ, or anti-TNF alone had essentially no effect on VCAM-1 expression.
  • Authors

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    Author List

  • Freedman DO; Parker-Cook S; Maia E Silva MC; Braga C; Maciel A
  • Start Page

  • 2901
  • End Page

  • 2908
  • Volume

  • 156
  • Issue

  • 8