Cl- channels are expressed in human normal monocytes: a functional role in migration, adhesion and volume change

M-J Kim1, G Cheng, D K Agrawal

  • 1Department of Biomedical Sciences, University School of Medicine, Omaha, NE 68178, USA.

Insights

Chloride channels in monocytes regulate their migration into blood vessels, a key step in vascular diseases like atherosclerosis. Blocking these channels inhibits monocyte movement and adhesion, offering potential therapeutic targets.

Area of Science:

  • * Cardiovascular Biology
  • * Cellular Physiology
  • * Immunology

Background:

  • * Monocyte adhesion and diapedesis are critical in occlusive vascular diseases such as atherosclerosis and restenosis.
  • * The precise mechanisms of monocyte transendothelial migration remain unclear.
  • * Ion channels are known to influence cell shape and volume, impacting cellular functions.

Purpose of the Study:

  • * To investigate the presence and function of chloride channels in human blood monocytes.
  • * To determine the role of these chloride channels in monocyte migration and adhesion.

Main Methods:

  • * Patch-clamp technique to measure whole-cell chloride currents in freshly isolated human monocytes.
  • * Use of specific chloride channel blockers: 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and IAA94.
  • * Boyden chemotactic chambers to assess monocyte chemotaxis and cell volume changes.

Main Results:

  • * Observed time-independent, outwardly rectifying whole-cell chloride currents in monocytes.
  • * Chloride channel blockers NPPB and IAA94 significantly attenuated these currents and inhibited monocyte chemotaxis.
  • * NPPB increased monocyte cell volume and decreased tumor necrosis factor-alpha-induced adhesion to endothelial cells.

Conclusions:

  • * Human monocytes express functional chloride channels.
  • * These chloride channels play a crucial role in regulating monocyte transendothelial migration, likely via cell volume modulation.
  • * Targeting monocyte chloride channels may offer a novel therapeutic strategy for occlusive vascular diseases.

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