PMID- 15918587
OWN - NLM
STAT- MEDLINE
DCOM- 20050708
LR  - 20181201
IS  - 0031-7144 (Print)
IS  - 0031-7144 (Linking)
VI  - 60
IP  - 5
DP  - 2005 May
TI  - Clozapine prevents apoptosis and enhances receptor-dependent respiratory burst in 
      human neutrophils.
PG  - 364-8
AB  - The present study was undertaken to determine if the antipsychotic drug clozapine 
      (CLZ) in the concentration range 2-50 microM can rescue polymorphonuclear cells 
      (PMNs) from undergoing apoptosis. Our results indicate that 20 microM CLZ can 
      rescue PMNs both from UVB-accelerated (28.0% vs. 45.9% for control without CLZ; P 
      < 0.05) and from spontaneous (35.8% vs. 57.6%; P < 0.05) apoptosis whereas 50 
      microM CLZ could rescue PMNs from spontaneous (34.3% vs. 57.6%; P < 0.05) 
      apoptosis only. Furthermore, since apoptosis has been reported to involve the 
      impairment of PMN function, we evaluated the effects of CLZ on respiratory burst 
      in UVB-irradiated and in unirradiated PMNs. When 20 or 50 microM CLZ-pretreated 
      PMNs were aged in a culture during 4 h, the luminol-dependent chemiluminescence 
      (CL) response was 3-fold (P < 0.01) and 2.5-fold (P < 0.05) increased, 
      respectively, by subsequent exposure to serum opsonized zymosan (OZ). When 50 
      microM-pretreated PMNs were either UVB-irradiated or unirradiated, the CL 
      response was 2.6-fold (P < 0.05) and 3.3-fold (P < 0.05) increased, respectively, 
      after subsequent exposure to formyl-methionyl-leucyl-phenylalanine (fMLP). In 
      contrast, the degree of enhancement was negligible upon subsequent exposure to 
      ionomycin or phorbol myristate acetate (PMA). When incubation times were extended 
      up to 22 h, the CL response induced by OZ in 20 microM CLZ-treated PMNs had a 
      4.9-fold increase (P < 0.001). This priming effect could be reverted when 20 
      microM CLZ-treated PMNs (aged 4 h in culture) were coincubated for 5 min with the 
      protein tyrosine kinase inhibitor genistein as well as with the 
      phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin. These findings 
      suggest that CLZ primes respiratory burst and prevents PMN apoptosis as a 
      consequence of tyrosine phosphorylation- and PI3-K activation-dependent signal 
      transduction pathways.
FAU - Vargas, F
AU  - Vargas F
AD  - Laboratorio de Fotoquimica, Centro de Quimica, Instituto Venezolano de 
      Investigaciones Cientificas I.V.I.C., Caracas. fvargas@ivic.ve
FAU - Rivas, C
AU  - Rivas C
FAU - Perdomo, H
AU  - Perdomo H
FAU - Rivas, A
AU  - Rivas A
FAU - Ojeda, L E
AU  - Ojeda LE
FAU - Velasquez, M
AU  - Velasquez M
FAU - Correia, H
AU  - Correia H
FAU - Hernandez, A
AU  - Hernandez A
FAU - Fraile, G
AU  - Fraile G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Pharmazie
JT  - Die Pharmazie
JID - 9800766
RN  - 0 (Androstadienes)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Growth Inhibitors)
RN  - 9010-72-4 (Zymosan)
RN  - DH2M523P0H (Genistein)
RN  - J60AR2IKIC (Clozapine)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Antipsychotic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Clozapine/*pharmacology
MH  - DNA Fragmentation
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Flow Cytometry
MH  - Genistein/pharmacology
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Luminescent Measurements
MH  - Neutrophils/*drug effects
MH  - Respiratory Burst/*drug effects
MH  - Ultraviolet Rays
MH  - Wortmannin
MH  - Zymosan/chemistry
EDAT- 2005/05/28 09:00
MHDA- 2005/07/09 09:00
CRDT- 2005/05/28 09:00
PHST- 2005/05/28 09:00 [pubmed]
PHST- 2005/07/09 09:00 [medline]
PHST- 2005/05/28 09:00 [entrez]
PST - ppublish
SO  - Pharmazie. 2005 May;60(5):364-8.