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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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A Flow Adhesion Assay to Study Leucocyte Recruitment to Human Hepatic Sinusoidal Endothelium Under Conditions of Shear Stress

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Binding of intercellular adhesion molecule 1 to β2-integrin regulates distinct cell adhesion processes on hepatic and

Chun-Fang Tong1, Yan Zhang1,2, Shou-Qin Lü1,2

  • 1Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences , Beijing , China.

American Journal of Physiology. Cell Physiology
|May 24, 2018
PubMed

Insights

Polymorphonuclear neutrophils (PMNs) use distinct β2-integrin kinetics to adhere to liver and brain endothelial cells. This study quantifies these biophysical differences, revealing tissue-specific regulation of PMN adhesion.

Area of Science:

  • Immunology
  • Cellular Biology
  • Biophysics

Background:

  • Polymorphonuclear neutrophils (PMNs) migrate to inflamed tissues by adhering to vascular endothelial cells.
  • This adhesion is primarily mediated by β2-integrins binding to ICAM-1.
  • Mechanisms of tissue-specific PMN recruitment, particularly in the liver versus brain, are not well understood.

Purpose of the Study:

  • To investigate the kinetic and mechanical mechanisms regulating tissue-specific recruitment of PMNs.
  • To compare the binding kinetics of β2-integrins (LFA-1 and Mac-1) to ICAM-1 on hepatic sinusoidal endothelial cells (LSECs) and cerebral endothelial cells (BMECs).

Main Methods:

  • Binding kinetics measurements of β2-integrins (LFA-1, Mac-1) with ICAM-1 on LSECs and BMECs.
  • In vitro free crawling tests of PMNs on LSEC and BMEC monolayers.
  • Numerical calculations and Monte Carlo simulations to model PMN crawling dynamics.

Main Results:

  • ICAM-1 on LSECs showed higher on- and off-rates but lower effective affinity for LFA-1 compared to Mac-1.
  • ICAM-1 on BMECs exhibited higher on-rates, similar off-rates, and higher effective affinity for LFA-1 compared to Mac-1.
  • In vitro PMN crawling assays confirmed these kinetics, demonstrating tissue-specific adhesion differences.

Conclusions:

  • The study quantifies the biophysical regulation of PMN adhesion in hepatic sinusoids versus cerebral endothelium.
  • β2-integrin-ICAM-1 binding kinetics significantly contribute to tissue-specific PMN recruitment.
  • This work provides a foundational understanding of differential immune cell trafficking mechanisms.
Keywords:
ICAM-1brainintegrinkineticsliver

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