Polymorphonuclear leukocyte transverse migration induces rapid alterations in endothelial focal contacts

Wen-Hong Su1, Hsiun-ing Chen, Chauying J Jen

  • 1Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, 701 Taiwan, ROC.

Insights

Transmigrating leukocytes (PMNs) disrupt endothelial cell focal contacts, altering cell-matrix interactions. This subendothelial migration impacts endothelial cells without triggering calcium signaling.

Area of Science:

  • Cell biology
  • Immunology
  • Vascular biology

Background:

  • Polymorphonuclear leukocytes (PMNs) migrate beneath endothelial cells (ECs) before tissue invasion.
  • The response of ECs to this subendothelial PMN migration is not well understood.

Purpose of the Study:

  • To investigate endothelial cell responses during PMN transverse migration.
  • To elucidate the molecular mechanisms of EC-PMN interactions in the subendothelial space.

Main Methods:

  • Utilized a tissue flow chamber to create an fMLP gradient.
  • Observed PMN transverse migration and EC responses in cultured cells and vascular tissues.
  • Analyzed changes in endothelial focal contact proteins (paxillin, FAK) and actin filaments.

Main Results:

  • Transmigrating PMNs directly contacted the basal side of ECs.
  • Paxillin rapidly disappeared from and reappeared in endothelial focal contacts as PMNs migrated.
  • FAK dephosphorylation and relocation occurred with prolonged PMN subendothelial presence.
  • PMN transverse migration did not induce endothelial calcium signaling.

Conclusions:

  • PMN transverse migration disrupts endothelial-matrix interactions.
  • Rapid, transient changes in endothelial focal contact composition occur during PMN subendothelial migration.
  • Endothelial cells exhibit distinct responses to transverse migration compared to transendothelial migration.

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