Inhibition of the neutrophil oxidative burst by sphingoid long-chain bases: role of protein kinase C in the activation of the burst

Journal Article · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5117441

Wilson, E; Olcott, M C; Bell, R M; Merrill, A H; Lambeth, J D

The neutrophil oxidative burst is triggered by a variety of both particulate (opsonized zymosan) and soluble agonists (formylmethionylleucylphenylalanine (FMLP), arachidonate, short-chained diacylglycerols (DAG) and phorbol myristate acetate (PMA)). The authors show that the long-chain lipid bases sphinganine and sphingosine block activation of the burst in human neutrophils. Inhibition is reversible, does not alter cell viability, and does not affect phagocytosis. The inhibition affects the activation mechanism rather than the NADPH-oxidase enzyme. The structural requirements for inhibition include a hydrophobic carbon chain and an amino-containing headgroup, and the naturally occurring erythro sphinganine was more potent than the threo isomer. Activation of the oxidative burst by a variety of agonists was blocked by the same concentration of sphinganine indicating a common inhibited step. The authors suggest that the common step is protein kinase C, as evidenced by the following: 1) long-chain bases inhibit PKC in a micelle reconstituted system, 2) PMA-induced phophorylation is inhibited by sphinganine, and 3) sphinganine competes with (/sup 3/H)-phorbol dibutyrate for its cytosolic receptor (i.e. protein kinase C). The authors suggest that sphingoid long-chain bases play a role in the cellular regulations.

• Research Organization: Emory Univ. School of Medicine, Atlanta, GA
• OSTI ID: 5117441
• Report Number(s): CONF-8606151-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
ENZYME ACTIVITY
ENZYMES
ESTERS
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
LIPIDS
MATERIALS
NEUTROPHILS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHORBOL ESTERS
PHOSPHOLIPIDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
SPHINGOMYELINS
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS