PMID- 11477284
OWN - NLM
STAT- MEDLINE
DCOM- 20010823
LR  - 20190513
IS  - 1462-0324 (Print)
IS  - 1462-0324 (Linking)
VI  - 40
IP  - 7
DP  - 2001 Jul
TI  - Inhibition of neutrophil responses by cyclosporin A. An insight into molecular 
      mechanisms.
PG  - 794-800
AB  - 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 Ca(2+) concentration 
      ([Ca(2+)]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 [Ca(2+)]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.
FAU - Spisani, S
AU  - Spisani S
AD  - Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, 
      Italy.
FAU - Fabbri, E
AU  - Fabbri E
FAU - Muccinelli, M
AU  - Muccinelli M
FAU - Cariani, A
AU  - Cariani A
FAU - Barbin, L
AU  - Barbin L
FAU - Trotta, F
AU  - Trotta F
FAU - Dovigo, L
AU  - Dovigo L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rheumatology (Oxford)
JT  - Rheumatology (Oxford, England)
JID - 100883501
RN  - 0 (Caseins)
RN  - 0 (Receptors, Peptide)
RN  - 11062-77-4 (Superoxides)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - 9010-72-4 (Zymosan)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Binding, Competitive
MH  - Calcium/metabolism
MH  - Caseins/pharmacology
MH  - Cell Degranulation/drug effects
MH  - Cell Survival/drug effects
MH  - Chemotaxis/drug effects/physiology
MH  - Cyclosporine/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/antagonists & inhibitors
MH  - Neutrophils/cytology/*drug effects/metabolism
MH  - Receptors, Peptide/metabolism
MH  - Respiratory Burst/drug effects
MH  - Superoxides/metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Zymosan/pharmacology
EDAT- 2001/07/31 10:00
MHDA- 2001/08/24 10:01
CRDT- 2001/07/31 10:00
PHST- 2001/07/31 10:00 [pubmed]
PHST- 2001/08/24 10:01 [medline]
PHST- 2001/07/31 10:00 [entrez]
AID - 10.1093/rheumatology/40.7.794 [doi]
PST - ppublish
SO  - Rheumatology (Oxford). 2001 Jul;40(7):794-800. doi: 
      10.1093/rheumatology/40.7.794.