Implications of a rise in cytosolic free calcium in the activation of RAW-264 macrophages for tumor cell killing |
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| Authors: | A M Gorecka-Tisera K W Snowdowne A B Borle |
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| Institution: | 1. Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 U.S.A.;2. Department of Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261 U.S.A.;1. Physiology Department, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China;2. Department of Pulmonary and Critical Care Medicine, Chifeng Municipal Hospital, Chifeng Clinical Medical School of Inner Mongolia Medical University, Inner Mongolia 204000, China;3. Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China;4. College of Acupuncture and Tuina, Anhui University of Chinese Medicine, Hefei, Anhui 230038, China;1. Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China;2. National and Local Joint Engineering Laboratory of Druggability and New Drugs Evaluation, Guangdong Engineering Laboratory of Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;1. Biomedical Research Institute, National Institute of Advance Industrial Science and Technology, Tsukuba, Ibaraki, Japan;2. Health Research Institute, National Institute of Advance Industrial Science and Technology, Takamatsu, Kagawa, Japan;3. Plant Research International, Wageningen University and Research Centre, Wageningen, the Netherlands;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo State, Nigeria;2. School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford, BD7 1DP, UK;1. Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guanzhou, 510280, Guangdong, People''s Republic of China;2. The Second Clinical Medical School, Zhujiang Hospital, Southern Medical University, Guanzhou, Guangdong, People''s Republic of China;3. Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, Southern Medical University, Guangzhou, Guangdong, People''s Republic of China |
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| Abstract: | The concentration of cytosolic-free calcium (Ca2+i) was determined with aequorin in RAW-264 macrophage-like cells activated in vitro for tumor cell killing with lymphokine (LK) and lipopolysaccharide (LPS). Treatments of these cells with optimal doses of stimulants, which evoked the development of cytolytic activity, also induced a rise in their Ca2+i. No rise in Ca2+i could be observed under treatments which failed to activate cells. The presence of both stimulants was an absolute requirement for evoking cytolytic activity and also a rise in Ca2+i. There was an apparent parallelism between the rate of activation and the rate of rise in Ca2+i. Cells which slowly developed their cytolytic activity exhibited a slow rise in Ca2+i, while macrophages which acquired their cytolytic activity at the faster rate also showed a more rapid increase in Ca2+i. The development of cytolytic activity in RAW-264 macrophages was inhibited by two intracellular calcium antagonists, TMB-8 and ruthenium red. This inhibition could be reversed by high concentrations of extracellular calcium. TMB-8, at the concentrations which were effective in inhibiting the activation process, also completely blocked the associated rise in Ca2+i. These results suggested that Ca2+i might play a role in the mechanism of tumoricidal transformation of RAW-264 macrophages. |
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