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A Flow Adhesion Assay to Study Leucocyte Recruitment to Human Hepatic Sinusoidal Endothelium Under Conditions of Shear Stress
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Adhesion molecules involved in hepoxilin A3-mediated neutrophil transepithelial migration

B P Hurley1, A Sin, B A McCormick

  • 1Mucosal Immunology Laboratory, Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, Boston, MA 02129, USA.

Clinical and Experimental Immunology
|November 17, 2007
PubMed

Insights

Hepoxilin A3 (HXA3) triggers neutrophil (PMN) migration differently than other chemoattractants, requiring specific adhesion molecules for crossing epithelial barriers. These findings impact drug development targeting inflammatory responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Inflammation Research

Background:

  • Neutrophil (PMN) migration across tissue barriers is crucial in inflammation.
  • Hepoxilin A3 (HXA3) is a PMN chemoattractant, but its interaction with PMNs during migration is poorly understood.
  • Understanding HXA3's role in PMN transepithelial migration is key to comprehending inflammatory processes.

Purpose of the Study:

  • To characterize HXA3-induced PMN transepithelial migration.
  • To identify adhesion molecules involved in HXA3-mediated migration across intestinal (T84) and airway (A549) epithelial cells.
  • To compare HXA3's adhesion profile with other chemoattractants like fMLP and LTB4.

Main Methods:

  • Investigated PMN transepithelial migration across T84 and A549 cell monolayers.
  • Utilized HXA3, fMLP, and LTB4 as chemoattractants.
  • Assessed the requirement of major surface adhesion molecules (CD18, CD47, CD44, CD55) for migration.

Main Results:

  • HXA3-induced PMN migration showed a distinct adhesion molecule profile compared to LTB4.
  • HXA3-induced migration critically depended on all four major adhesion molecules examined (CD18, CD47, CD44, CD55).
  • The chemoattractant gradient and epithelial cell type influenced the adhesion molecules involved.

Conclusions:

  • The chemoattractant type and epithelial cell layer dictate the adhesion molecules essential for PMN transepithelial migration.
  • HXA3 utilizes a unique set of adhesion molecules for PMN migration, differing from LTB4.
  • These findings are significant for developing targeted therapies for inflammatory diseases by identifying potential drug targets.

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