title: Store-operated Ca²⁺ entry mediated regulation of polarization in differentiated human neutrophil-like HL-60 cells under hypoxia.
abstract: The regulation of neutrophil polarization by calcium entry is critical for maintaining an effective host response. Hypoxia has a major effect on the apoptosis of neutrophils, however the role of store-operated Ca2+ entry (SOCE) in neutrophil polarization under hypoxia remains to be elucidated. In the present study, we examined the polarization of differentiated human neutrophil-like HL-60 (dHL-60) cells exposed to hypoxia (3% O2) and the results demonstrated that the percentage of polarized cells following exposure to an N-formyl-Met-Leu-Phe (fMLP) gradient in the Zigmond chamber was increased. We examined stromal interaction molecule 1 (STIM1) and Orai1 expression in dHL-60 cells during hypoxia, and it was observed that the expression of STIM1 and Orai1 was significantly reduced at day 2. However, no apparent change was observed on the first day, indicating that this effect is dependent on stimulation time. Fluo-4/acetoxymethyl (AM) ester imaging also demonstrated that SOCE was decreased in dHL-60 cells. The plasmid overexpression assay demonstrated that the response of polarization was returned to the control level. We demonstrated the inhibitory role of SOCE on the polarization of dHL-60 cells under hypoxic conditions, which may be the mechanism for the adaptation of neutrophils to hypoxia. SOCE is also suggested to be a key modulator of immune deficiency under hypoxic conditions and is potentially a therapeutic target.
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Qinghai University, Xining, Qinghai 810000, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Cai
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Qinghai University, Xining, Qinghai 810000, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Qinghai University, Xining, Qinghai 810000, P.R. China.
authors.forename: Zhengzhong
authors.initials: Z
authors.lastname: Bai
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Qinghai University, Xining, Qinghai 810000, P.R. China.
authors.forename: Rili
authors.initials: R
authors.lastname: Ge
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D005786:Gene Expression Regulation; D018922:HL-60 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium