Mechanisms of leukotriene B-4-triggered monocyte adhesion

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Objective - Leukotriene B-4 (LTB4) has been implicated in the trafficking of monocytes to inflammatory pathologicconditions, such as transplant rejection and atherosclerosis. The aim of this study was to determine the mechanisms by which LTB4 contributes to monocyte capture from the circulation. Methods and Results - In in vitro and in vivo vascular models, the lipid chemoattractant LTB4 was an equipotent agonist of monocyte adhesion compared with the chemokine monocyte chemoattractant protein-1 (MCP-1). Adenoviral gene transfer of specific endothelial adhesion molecules and blocking monoclonal antibody studies demonstrated that LTB4 triggers both beta(1)- and beta(2)-integrin-dependent adhesion. Flow cytometry studies suggested that changes in integrin avidity or affinity, rather than alterations of integrin surface expression, were responsible for the chemoattractant-triggered arrest. Surprisingly, in contrast to the peptide chemokine MCP-1, LTB4 did not activate the phosphoinositide 3-kinase pathway, which is a functionally critical step in chemokine-triggered effector functions. Conclusions - LTB4 is a potent trigger of monocyte adhesion under flow yet mediates its effects via pathways that appear to differ from peptide chemoattractants. A better understanding of the mechanisms of LTB4-induced monocyte trafficking might shed insight into disease pathogenesis and pinpoint critical steps for therapeutic intervention for multiple human inflammatory pathologic conditions.

Detaljer

Författare
  • EB Friedrich
  • AM Tager
  • E Liu
  • Annika Pettersson
  • Christer Owman
  • L Munn
  • AD Luster
  • RE Gerszten
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi
Originalspråkengelska
Sidor (från-till)1761-1767
TidskriftArteriosclerosis, Thrombosis and Vascular Biology
Volym23
Utgivningsnummer10
StatusPublished - 2003
PublikationskategoriForskning
Peer review utfördJa