PMID- 2825597
OWN - NLM
STAT- MEDLINE
DCOM- 19871228
LR  - 20190628
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 259
IP  - 1
DP  - 1987 Nov 15
TI  - Protein kinase C inhibition by sphingoid long-chain bases: effects on secretion 
      in human neutrophils.
PG  - 204-14
AB  - Sphingoid long-chain bases (sphinganine and sphingosine) have recently been shown 
      to inhibit protein kinase C both in vitro [Y. Hannun et al. (1986) J. Biol. Chem. 
      261, 12604-12609] and in intact human neutrophils, in which they block activation 
      of the superoxide-generating respiratory burst [E. Wilson et al. (1986) J. Biol. 
      Chem. 261, 12616-12623]. In the present study we have used sphingosine to 
      investigate the pathways for agonist-induced secretion of neutrophil granule 
      contents. Induction of secretion of the specific granule component lactoferrin by 
      a variety of agonists [phorbol 12-myristate-13-acetate (PMA), 
      formyl-methionyl-leucyl-phenylalanine (fMLP), and calcium ionophore A23187] was 
      completely inhibited by sphingosine with an ED50 of 6 to 10 microM. PMA-induced 
      secretion of lysozyme (present in both the azurophilic and specific granules) was 
      completely blocked with an ED50 of 10 microM, whereas fMLP-induced secretion was 
      only about 50% inhibited. Secretion of the azurophilic granule proteins 
      beta-glucuronidase and myeloperoxidase was activated by fMLP and A23187, but not 
      by PMA, and was not affected by sphingosine. The use of A23187 in the presence of 
      sphingosine allowed differentiation between calcium activation of protein kinase 
      C-dependent versus-independent pathways. The effect of sphingosine was not 
      mediated by neutralizing intracellular acidic compartments, since treatment of 
      neutrophils with inhibitory concentrations of sphingosine did not significantly 
      alter the uptake of labeled methylamine. We conclude that at least two mechanisms 
      participate in the regulation of specific and azurophilic granule secretion, 
      respectively: a protein kinase C-dependent pathway and a calcium-dependent 
      pathway which does not involve protein kinase C.
FAU - Wilson, E
AU  - Wilson E
AD  - Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 
      30322.
FAU - Rice, W G
AU  - Rice WG
FAU - Kinkade, J M Jr
AU  - Kinkade JM Jr
FAU - Merrill, A H Jr
AU  - Merrill AH Jr
FAU - Arnold, R R
AU  - Arnold RR
FAU - Lambeth, J D
AU  - Lambeth JD
LA  - eng
GR  - AI22809/AI/NIAID NIH HHS/United States
GR  - CA22294/CA/NCI NIH HHS/United States
GR  - CA46508/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 37H9VM9WZL (Calcimycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.4.21.- (Lactoferrin)
RN  - NGZ37HRE42 (Sphingosine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - OWA98U788S (safingol)
SB  - IM
MH  - Calcimycin/pharmacology
MH  - Glucuronidase/blood/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Lactoferrin/blood/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*enzymology
MH  - Peroxidase/blood/metabolism
MH  - Protein Kinase C/antagonists & inhibitors/*blood
MH  - Sphingosine/*analogs & derivatives/*pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
EDAT- 1987/11/15 00:00
MHDA- 2001/03/28 10:01
CRDT- 1987/11/15 00:00
PHST- 1987/11/15 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1987/11/15 00:00 [entrez]
AID - 0003-9861(87)90487-5 [pii]
AID - 10.1016/0003-9861(87)90487-5 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 1987 Nov 15;259(1):204-14. doi: 
      10.1016/0003-9861(87)90487-5.