Reversible activation of the neutrophil superoxide generating system by hexachlorocyclohexane: correlation with effects on a subcellular superoxide-generating fraction

Journal Article · Tue Jul 01 04:00:00 EDT 1986 · J. Immunol.; (United States)

OSTI ID:5447731

English, D; Schell, M; Siakotos, A; Gabig, T G

..gamma..-hexachlorocyclohexane was found to exert profound effects on the phosphatidylinositol cycle, cytosolic calcium level, and the respiratory burst of human neutrophils. Exposure of neutrophils prelabelled with /sup 32/P to 4 x 10/sup -4/ M ..gamma..-hexachlorocyclohexane almost tripled radioactivity in phosphatidic acid and correspondingly decreased radioactivity in phosphatidylinositol 4,5 bisphosphate. Under similar conditions, ..gamma..-hexachlorocyclohexane evoked the generation of superoxide at a rate of over 11 nmol/min/10/sup 6/ cells and more than doubled cytosolic-free calcium concentration as monitored by Quin-2 fluorescence. Because intermediates of the phosphatidylinositol cycle, via increases in available calcium levels or activated protein kinase C, are considered potential second messenger for activation of the NADPH-dependent O/sub 2//sup -/-generating system, neutrophil responses to ..gamma..-hexachlorocyclohexane were compared with responses to phorbol myristate acetate, an activator of protein kinase C with well known effects on neutrophils. Like phorbol myristate acetate, ..gamma..-hexachlorocyclohexane induced neutrophil degranulation but was not an effective chemotactic stimulus. The ability of ..gamma..-hexachlorocyclohexane to induce a pattern of oxidative activation in neutrophil cytoplasts similar to that n intact cells indicated that concurrent degranulation was not required for sustained O/sub 2//sup -/ generation in response to this agent.

• Research Organization: Indiana Univ. School of Medicine, Indianapolis
• OSTI ID: 5447731
• Journal Information: J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 137:1; ISSN JOIMA
• Country of Publication: United States
• Language: English

Related Subjects

550301 -- Cytology-- 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.
ALKALINE EARTH METALS
ANIMALS
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM
CARCINOGENS
CHEMICAL ACTIVATION
CHLORINATED AROMATIC HYDROCARBONS
DAYS LIVING RADIOISOTOPES
ELEMENTS
ENZYMES
ESTERS
HALOGENATED AROMATIC HYDROCARBONS
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
MAMMALS
MAN
MATERIALS
METALS
NEUTROPHILS
NUCLEI
ODD-ODD NUCLEI
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
PHORBOL ESTERS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
RADICALS
RADIOISOTOPES
SUPEROXIDE RADICALS
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES