PMID- 1874738
OWN - NLM
STAT- MEDLINE
DCOM- 19910926
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 266
IP  - 24
DP  - 1991 Aug 25
TI  - The chymotrypsin inhibitor carbobenzyloxy-leucine-tyrosine-chloromethylketone 
      interferes with phospholipase D activation induced by 
      formyl-methionyl-leucyl-phenylalanine in human neutrophils.
PG  - 15870-5
AB  - The effects of carbobenzyloxy-leucine-tyrosine-chloromethylketone (zLYCK), an 
      inhibitor of chymotrypsin-like proteases, on signal transduction in human 
      neutrophils triggered by the chemoattractant 
      formyl-methionyl-leucyl-phenylalanine (fMLP) were investigated. zLYCK (10 microM) 
      inhibited the fMLP-induced respiratory burst in neutrophils treated with 
      cytochalasin B. In the presence of zLYCK (10 microM), the activation of 
      phospholipase D in response to fMLP addition was inhibited. zLYCK did not inhibit 
      the binding of [3H] fMLP to its receptor or the enzymic activity of phospholipase 
      D because the response to ionomycin was unaffected. The effect of zLYCK on 
      phospholipase D correlated well with its effects on the accumulation of 
      diglycerides, which was also inhibited in the presence of zLYCK. In 
      electropermeabilized neutrophils, too, zLYCK caused an inhibition of the 
      fMLP-induced respiratory burst and the fMLP-induced activation of phospholipase 
      D. Interestingly, this inhibition could be bypassed by guanosine 
      5'-O-(thiotriphosphate). We conclude that the inhibition of the respiratory burst 
      in human neutrophils by zLYCK is caused by the selective inhibition of signal 
      transduction leading to activation of phospholipase D and that zLYCK might be a 
      useful probe to study the role of phospholipase D in neutrophil activation.
FAU - Kessels, G C
AU  - Kessels GC
AD  - Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, 
      Amsterdam.
FAU - Gervaix, A
AU  - Gervaix A
FAU - Lew, P D
AU  - Lew PD
FAU - Verhoeven, A J
AU  - Verhoeven AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Diglycerides)
RN  - 0 (Glycerophospholipids)
RN  - 0 (Phosphatidic Acids)
RN  - 0 (phosphatidylethanol)
RN  - 56979-35-2 (carbobenzyloxyleucyl-tyrosine chloromethyl ketone)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - EC 3.4.21.1 (Chymotrypsin)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/*pharmacology
MH  - Chymotrypsin/*antagonists & inhibitors
MH  - Diglycerides/metabolism
MH  - Enzyme Activation/drug effects
MH  - *Glycerophospholipids
MH  - Humans
MH  - N-Formylmethionine Leucyl-Phenylalanine/metabolism/*pharmacology
MH  - Neutrophils/drug effects/*enzymology
MH  - Oxygen/metabolism
MH  - Phosphatidic Acids/biosynthesis
MH  - Phospholipase D/*metabolism
MH  - Signal Transduction
EDAT- 1991/08/25 00:00
MHDA- 1991/08/25 00:01
CRDT- 1991/08/25 00:00
PHST- 1991/08/25 00:00 [pubmed]
PHST- 1991/08/25 00:01 [medline]
PHST- 1991/08/25 00:00 [entrez]
AID - S0021-9258(18)98489-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1991 Aug 25;266(24):15870-5.