PMID- 8834862
OWN - NLM
STAT- MEDLINE
DCOM- 19961205
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 104
IP  - 1
DP  - 1996 Jan
TI  - Phospholipase A2 is involved in the mechanism of activation of neutrophils by 
      polychlorinated biphenyls.
PG  - 52-8
AB  - Aroclor 1242, a mixture of polychlorinated biphenyls (PCBs), activates 
      neutrophils to produce superoxide anion (O2-) by a mechanism that involves 
      phospholipase C-dependent hydrolysis of membrane phosphoinositides; however, 
      subsequent signal transduction mechanisms are unknown. We undertook this study to 
      determine whether phospholipase A2-dependent release of arachidonic acid is 
      involved in PCB-induced O2- production. We measured O2- production in vitro in 
      glycogen-elicited, rat neutrophils in the presence and absence of the inhibitors 
      of phospholipase A2: quinacrine, 4-bromophenacyl bromide (BPB), and manoalide. 
      All three agents significantly decreased the amount of O2- detected during 
      stimulation of neutrophils with Aroclor 1242. Similar inhibition occurred when 
      neutrophils were activated with the classical stimuli, 
      formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate. The 
      effects of BPB and manoalide were not a result of cytotoxicity or other 
      nonspecific effects, although data suggest that quinacrine is an O2- scavenger. 
      Significant release of 3H-arachidonic acid preceded O2- production in neutrophils 
      stimulated with Aroclor 1242 or fMLP. Manoalide, at a concentration that 
      abolished O2- production, also inhibited the release of 3H-arachidonate. Aspirin, 
      zileuton, or WEB 2086 did not affect Aroclor 1242-induced O2- production, 
      suggesting that eicosanoids and platelet-activating factor are not needed for 
      neutrophil activation by PCBs. Activation of phospholipase A2 and O2- production 
      do not appear to involve the Ah receptor because a congener with low affinity, 
      but not one with high affinity for this receptor, stimulated the release of 
      arachidonic acid and O2-. These data suggest that Aroclor 1242 stimulates 
      neutrophils to produce O2- by a mechanism that involves phospholipase 
      A2-dependent release of arachidonic acid.
FAU - Tithof, P K
AU  - Tithof PK
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing 48824, USA.
FAU - Schiamberg, E
AU  - Schiamberg E
FAU - Peters-Golden, M
AU  - Peters-Golden M
FAU - Ganey, P E
AU  - Ganey PE
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Aroclors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (Terpenes)
RN  - 11062-77-4 (Superoxides)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 53469-21-9 (aroclor 1242)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - E1DK0157K9 (manoalide)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - H0C805XYDE (Quinacrine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - R16CO5Y76E (Aspirin)
RN  - V1L22WVE2S (zileuton)
RN  - X6Q56QN5QC (Hydroxyurea)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/*metabolism
MH  - Aroclors/pharmacology
MH  - Aspirin/pharmacology
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Hydroxyurea/analogs & derivatives/pharmacology
MH  - In Vitro Techniques
MH  - Lipoxygenase Inhibitors/pharmacology
MH  - Male
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophil Activation
MH  - Neutrophils/*drug effects/metabolism
MH  - Phospholipases A/antagonists & inhibitors/*metabolism
MH  - Phospholipases A2
MH  - Polychlorinated Biphenyls/pharmacology/*toxicity
MH  - Quinacrine/pharmacology
MH  - Rats
MH  - Superoxides/*metabolism
MH  - Terpenes/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
PMC - PMC1469247
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
PMCR- 1996/01/01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
PHST- 1996/01/01 00:00 [pmc-release]
AID - 10.1289/ehp.9610452 [doi]
PST - ppublish
SO  - Environ Health Perspect. 1996 Jan;104(1):52-8. doi: 10.1289/ehp.9610452.