Requirement for both receptor-operated and store-operated calcium entry in N-formyl-methionine-leucine-phenylalanine-induced neutrophil polarization |
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| Authors: | Chunqing Cai Shihao Tang Xubu Wang Shaoxi Cai Xiaojing Meng Wenying Zou Fei Zou |
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| Affiliation: | 1. Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China;2. Department of Respiratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China;1. Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;2. Pulmonary Injury and Repair Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA;3. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294,USA;4. Center for Free Radical Biology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA;5. Veterans Administration Medical Center, Birmingham, AL 35233, USA;1. Engineering Research Center of Groundwater Pollution Control and Remediation, Ministry of Education, College of Water Sciences, Beijing Normal University, Beijing 100875, China;2. Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China;1. Department of Otorhinolaryngology – Head and Neck Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan;2. Department of Neuroscience and Cell Biology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan;3. Department of Otolaryngology – Head and Neck Surgery, Osaka National Medical Center, 2-1-14 Hoenzaka, Chuo-ku, Osaka 540-0006, Japan;1. Molecular-, Cellular- and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, 53115 Bonn, Germany;2. Molecular Therapeutics, School of Pharmacy, Medical Biology Centre, Queen''s University, Belfast BT7 1NN Northern Ireland;3. Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ Scotland;4. Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Faculty of Medicine, University of New South Wales, Darlinghurst, NSW 2010, Australia;5. Pharmacology and Toxicology, University of Bonn, 53347 Bonn, Germany;6. Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense M, Denmark;7. Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA;1. Department of Medical Research, Taichung Veterans General Hospital, 160, Sec.3, Chung Kang Road, Taichung 407, Taiwan, ROC;2. Division of Infectious Diseases, Department of Internal Medicine, Changhua Show Chwan Memorial Hospital, Changhua 500, Taiwan, ROC;3. Department of Biochemistry, China Medical University, Taichung 404, Taiwan, ROC |
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| Abstract: | Tissue penetration of neutrophils is a key process in many inflammatory diseases. In response to inflammatory stimuli such as N-formyl-methionine-leucine-phenylalanine (fMLP), neutrophils polarize and migrate towards the chemotactic gradient of the stimulus. Elevated intracellular Ca2+ concentration is known to play a critical role in neutrophil polarization and migration; however, the exact mechanism remains elusive. Here, we demonstrated that fMLP stimulation caused not only store-operated calcium entry (SOCE), but also receptor-operated calcium entry (ROCE) in neutrophils by using both pharmacological and neutralizing monoclonal antibody approaches. We also investigated neither Rac2 nor Cdc42 activation could take place if either SOCE or ROCE was inhibited. This study thus provides the first evidence for coordination of Ca2+ influx by SOCE and ROCE to regulate neutrophil polarization. |
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