ATRA treatment slowed P-selectin-mediated rolling of flowing HL60 cells in a mechano-chemical-dependent manner

Frontiers in Immunology

Immunology

Ying Fang¹  Quhuan Li¹  Wenjian Tu¹  Xiaoxi Sun¹  Xiaoting Dong¹  Shiping Peng¹  Jianhua Wu¹  Yingchen Ling¹  Bing Huang² 

[1] Institute of Mechanics/School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China;Institute of Mechanics/School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China;Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China;

关键词: HL60 cell;    neutrophils;    ATRA;    differentiation;    cell adhesion;    fluid shear stress;    APL DS;   

DOI  :  10.3389/fimmu.2023.1148543

 received in 2023-01-27, accepted in 2023-04-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

All-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) toward granulocytes may trigger APL differentiation syndrome (DS), but there is less knowledge about the mechano-chemical regulation mechanism of APL DS under the mechano-microenvironment. We found that ATRA-induced changes in proliferation, morphology, and adhesive molecule expression levels were either dose or stimulus time dependent. An optimal ATRA stimulus condition for differentiating HL60 cells toward neutrophils consisted of 1 × 10-6 M dose and 120 h of stimulus time. Under wall shear stresses, catch–slip bond transition governs P-selectin-mediated rolling for neutrophils and untreated or ATRA-treated (1 × 10-6 M, 120 h) HL60 cells. The ATRA stimuli slowed down the rolling of HL60 cells on immobilized P-selectin no matter whether ICAM-1 was engaged. The β2 integrin near the PSGL-1/P-selectin axis would be activated within sub-seconds for each cell group mentioned above, thus contributing to slow rolling. A faster β2 integrin activation rate and the higher expression levels of PSGL-1 and LFA-1 were assigned to induce the over-enhancement of ATRA-treated HL60 adhesion in flow, causing APL DS development. These findings provided an insight into the mechanical–chemical regulation for APL DS development via ATRA treatment of leukemia and a novel therapeutic strategy for APL DS through targeting the relevant adhesion molecules.

【 授权许可】

Unknown   
Copyright © 2023 Dong, Peng, Ling, Huang, Tu, Sun, Li, Fang and Wu