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Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
09:16

Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro

Published on: November 26, 2018

Monocytes initiate a cycle of leukocyte recruitment when cocultured with endothelial cells

Andreas Tsouknos1, Gerard B Nash, G Ed Rainger

  • 1The Department of Physiology, Cardiovascular Rheology Group, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK.

Atherosclerosis
|September 6, 2003
PubMed

Insights

Monocytes activate endothelial cells (EC) to recruit more leukocytes, contributing to chronic inflammation and potentially initiating a self-perpetuating cycle relevant to atherosclerosis. This monocyte-EC interaction drives leukocyte adhesion and transmigration.

Area of Science:

  • Immunology
  • Cell Biology
  • Cardiovascular Research

Background:

  • Monocyte and T-lymphocyte recruitment to the arterial intima is crucial in atherosclerotic plaque development.
  • Endothelial cell (EC) activation, involving adhesion receptors and chemokines, mediates this leukocyte recruitment.
  • Chronic arterial inflammation is a hallmark of atherosclerosis.

Purpose of the Study:

  • To investigate if monocytes can activate cocultured EC to support further leukocyte adhesion, activation, and transmigration.
  • To determine the role of specific adhesion molecules (E-selectin, P-selectin, VCAM-1) in monocyte-induced EC activation over time.
  • To explore the potential of this EC activation mechanism in initiating self-perpetuating inflammatory cycles relevant to atherogenesis.

Main Methods:

  • Coculture of monocytes and endothelial cells (EC).
  • Assessment of leukocyte adhesion, activation, and transmigration on activated EC.
  • Use of blocking antibodies against E-selectin, P-selectin, and vascular cell adhesion molecule-1 (VCAM-1) at different time points (4h and 24h).
  • Immunofluorescence analysis to confirm endothelial expression of adhesion molecules.

Main Results:

  • Monocytes activated cocultured EC to support adhesion, activation, and transmigration of a secondary monocyte/lymphocyte bolus.
  • Leukocyte adhesion and behavior on monocyte-activated EC were comparable to EC activated by tumor necrosis factor-alpha (TNF-alpha).
  • At 4h, E-selectin, P-selectin, and VCAM-1 mediated adhesion; at 24h, E-selectin and VCAM-1 were primarily involved, with P-selectin playing a lesser role.
  • Monocyte coculture induced significant endothelial expression of E-selectin and VCAM-1.

Conclusions:

  • Endothelial cells stimulated by monocytes can effectively support the adhesion of flowing mononuclear leukocytes.
  • This monocyte-induced EC activation and subsequent leukocyte recruitment may represent a self-perpetuating inflammatory mechanism.
  • This process could be a significant factor in the pathogenesis of atherosclerosis and other chronic inflammatory diseases.

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