PMID- 19548361
OWN - NLM
STAT- MEDLINE
DCOM- 20090721
LR  - 20211020
IS  - 0893-228X (Print)
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 21
IP  - 12
DP  - 2008 Dec
TI  - Effects of acrolein on leukotriene biosynthesis in human neutrophils.
PG  - 2424-32
AB  - Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is 
      present in high concentrations in cigarette smoke. In the current study, the 
      effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was 
      examined. Eicosanoid synthesis in neutrophils was initiated by priming with 
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent 
      stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase 
      (5-LO) products in addition to small amounts of cyclooxygenase (COX) products 
      were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO 
      products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 
      microM) was present with almost complete inhibition at > or = 25 microM acrolein. 
      The production of COX products was not affected by acrolein in these cells. The 
      effect of acrolein was examined on key parts of the eicosanoid pathway, such as 
      arachidonic acid release, intracellular calcium ion concentration, and adenosine 
      production. In addition, the direct effect of acrolein on 5-LO enzymatic activity 
      was probed using a recombinant enzyme. Some of these factors were affected by 
      acrolein but did not completely explain the almost complete inhibition of 5-LO 
      product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the 
      effect of acrolein on different stimuli that initiate the 5-LO pathway 
      [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and 
      A23187] was examined. Acrolein had no significant effect on the leukotriene 
      production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. 
      Additionally, 50% inhibition of the 5-LO pathway was observed in 
      A23187-stimulated neutrophils. Our results suggest that acrolein has a profound 
      effect on the 5-LO pathway in neutrophils, which may have implications in disease 
      states, such as chronic obstructive pulmonary disease and other pulmonary 
      disease, where both activated neutrophils and acrolein are present.
FAU - Berry, Karin A Zemski
AU  - Berry KA
AD  - Department of Pharmacology, MSC 8303, University of Colorado Denver, RC1 South, 
      L18-6120, 12801 East 17th Avenue, P.O. Box 6511, Aurora, Colorado 80045, USA.
FAU - Henson, Peter M
AU  - Henson PM
FAU - Murphy, Robert C
AU  - Murphy RC
LA  - eng
GR  - P01 HL034303/HL/NHLBI NIH HHS/United States
GR  - P01 HL034303-240004/HL/NHLBI NIH HHS/United States
GR  - HL034303/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Air Pollutants)
RN  - 0 (Leukotrienes)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Platelet Activating Factor)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 7864XYD3JJ (Acrolein)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
SB  - IM
MH  - Acrolein/*toxicity
MH  - Air Pollutants/*toxicity
MH  - Arachidonate 5-Lipoxygenase/metabolism
MH  - Calcimycin/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Humans
MH  - Leukotrienes/*biosynthesis
MH  - Lipoxygenase Inhibitors
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*drug effects/metabolism
MH  - Platelet Activating Factor/pharmacology
MH  - Prostaglandin-Endoperoxide Synthases/metabolism
PMC - PMC2772067
MID - NIHMS86489
EDAT- 2009/06/24 09:00
MHDA- 2009/07/22 09:00
PMCR- 2009/12/01
CRDT- 2009/06/24 09:00
PHST- 2009/06/24 09:00 [entrez]
PHST- 2009/06/24 09:00 [pubmed]
PHST- 2009/07/22 09:00 [medline]
PHST- 2009/12/01 00:00 [pmc-release]
AID - 10.1021/tx800333u [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2008 Dec;21(12):2424-32. doi: 10.1021/tx800333u.