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Rheumatology 2001; 40: 794-800
© 2001 British Society for Rheumatology
Original Papers |
Inhibition of neutrophil responses by cyclosporin A. An insight into molecular mechanisms
Department of Biochemistry and Molecular Biology,
1 Department of Biology, Section of General Physiology, University of Ferrara,
2 Department of Biology, University of Bologna and
3 Division of Rheumatology, Arcispedale S. Anna, Ferrara, Italy
Objective. Cyclosporin A (CsA) is an effective agent in rheumatoid arthritis (RA), slowing joint damage progression. Its therapeutic effect on T lymphocytes has been studied extensively, but there is little information available about neutrophils, the cells responsible for a substantial proportion of inflammation. A study was performed to investigate the in vitro effects of CsA on neutrophil functions triggered by several agonists and determine whether the drug could counteract the binding of formyl-methionyl-leucyl-phenylalanine (fMLP) to its receptor and/or modulate changes in the intracellular Ca2+ concentration ([Ca2+]i).
Methods. CsA was added to neutrophils 5–50 min before the incubation steps for neutrophil function assays (chemotaxis, superoxide anion production, lysozyme release), calcium measurements and receptor binding experiments.
Results. CsA appeared to be particularly effective in lowering chemotaxis, superoxide anion production and lysozyme release induced by different agonists. However, it did not significantly affect either basal or agonist-stimulated neutrophil [Ca2+]i and the interaction between fMLP and its receptor.
Conclusions. Because of its in vitro inhibition of neutrophil functions, CsA appears to have considerable potential as an anti-inflammatory drug. Moreover, as it is also a potent immunosuppressive agent, it may reduce the progression of joint damage in RA. More work remains to be done to clarify the molecular mechanism of CsA action on neutrophils.
KEY WORDS: CsA, Rheumatoid arthritis, Neutrophil functionality, Cytosolic calcium, Receptor binding assay.
Correspondence to: L. Dovigo, Division of Rheumatology, Arcispedale S. Anna, C.so della Giovecca 203, 44100 Ferrara, Italy
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