Modulation of alveolar macrophage lipoxygenase metabolism by the sulfhydryl-reactive compound

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5388960

Peters-Golden, M; Thebert, P

N-ethylmaleimide (NEM), a sulfhydryl(SH)-reactive compound, has been previously shown to trigger arachidonic acid (AA) release and thromboxane (TxB/sub 2/) synthesis in alveolar macrophages (AMs). The present study was undertaken to characterize the effects of this agent on rat AM lipoxygenase metabolism. NEM caused dose-dependent stimulation of TxB/sub 2/ and, to a lesser extent, PGE/sub 2/ synthesis. However, NEM at either 5 or 10 ..mu..M failed to stimulate production of LTB/sub 4/ (control= 31 + 6, 5 ..mu..M = 36 + 8, 10 ..mu..M = 39 +/- 14 pg/ml; mean + SEM, n = 3) or LTC/sub 4/ (control = 109 +/- 29, 5 ..mu..M = 111 + 27, 10 ..mu..M = 113 +/- 40 pg/ml; n = 4). Indomethacin (5 ..mu..M) failed to shunt AA towards LTB/sub 4/ or LTC/sub 4/ synthesis in response to 10 ..mu..M NEM. In addition, /sup 14/C-5-HETE production by /sup 14/C-AA prelabeled AMs was no greater in NEM-treated cultures (308 +/- 96 cpm) than in control cultures (321 +/- 159 cpm/4 x 10/sup 6/ cells). The effect of NEM on zymosan-induced eicosanoid synthesis was examined by incubating AMs with zymosan (100 ..mu..g/ml) for 1 hour + NEM. NEM (10 ..mu..M) inhibited zymosan-induced LTC/sub 4/ synthesis (control = 122 +/- 43, zymosan = 266 +/- 35, zymosan + NEM = 105 +/- 38 pg/ml; n = 3; p = .05) without cytotoxicity, and while yielding additive increments in TxB/sub 2/ and PGE/sub 2/. Since the actions of both 5-lipoxygenase and glutathione transferase represent SH-dependent steps in the synthesis of LTs, it is postulated that the SH reactivity of NEM explains both its inability to stimulate LT synthesis and its ability to inhibit zymosan-induced LTC/sub 4/ synthesis.

• Research Organization: Univ. of Michigan, Ann Arbor
• OSTI ID: 5388960
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTIMITOTIC DRUGS
ARACHIDONIC ACID
BIOLOGICAL EFFECTS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
IMIDES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MACROPHAGES
MAMMALS
METABOLISM
MONOCARBOXYLIC ACIDS
NEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
OXYGENASES
PHAGOCYTES
RADIOSENSITIZERS
RATS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES
ZYMOSAN