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

Author:

Tong Chun-Fang1,Zhang Yan12,Lü Shou-Qin12,Li Ning1,Gong Yi-Xin1,Yang Hao1,Feng Shi-Liang1,Du Yu1,Huang Dan-Dan1,Long Mian12

Affiliation:

1. Center 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

2. School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China

Abstract

Flowing polymorphonuclear neutrophils (PMNs) are forced to recruit toward inflamed tissue and adhere to vascular endothelial cells, which is primarily mediated by the binding of β2-integrins to ICAM-1. This process is distinct among different organs such as liver and brain; however, the underlying kinetic and mechanical mechanisms regulating tissue-specific recruitment of PMNs remain unclear. Here, binding kinetics measurement showed that ICAM-1 on murine hepatic sinusoidal endothelial cells (LSECs) bound to lymphocyte function-associated antigen-1 (LFA-1) with higher on- and off-rates but lower effective affinity compared with macrophage-1 antigen (Mac-1), whereas ICAM-1 on cerebral endothelial cells (BMECs or bEnd.3 cells) bound to LFA-1 with higher on-rates, similar off-rates, and higher effective affinity compared with Mac-1. Physiologically, free crawling tests of PMN onto LSEC, BMEC, or bEnd.3 monolayers were consistent with those kinetics differences between two β2-integrins interacting with hepatic sinusoid or cerebral endothelium. Numerical calculations and Monte Carlo simulations validated tissue-specific contributions of β2-integrin-ICAM-1 kinetics to PMN crawling on hepatic sinusoid or cerebral endothelium. Thus, this work first quantified the biophysical regulation of PMN adhesion in hepatic sinusoids compared with cerebral endothelium.

Funder

National Natural Science Foundation of China (NSFC)

Chinese Academy of Sciences Strategic Priority Research Program

Frontier Science Key Project

National Key Research and Development of China

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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