Kinetics of phospholipase A2, arachidonic acid, and eicosanoid appearance in mouse zymosan peritonitis.
Intraperitoneal injection of zymosan into mice induces a peritonitis characterized by cellular influx, plasma leakage and the appearance of arachidonic acid (AA) metabolites. We report that zymosan injection also stimulates the accumulation of AA, docosahexaenoic acid, linoleic acid, and phospholipase A2 (PLA2) activity. The amount of the unsaturated fatty acids (UnFA) varies both with the zymosan dose and time. Significantly increased levels of UnFA were first detected 15 min after zymosan injection. Maximal levels of the UnFA were reached 1 to 2 h post zymosan injection (AA: 725 +/- 29 ng/mouse, docosahexaenoic acid: 296 +/- 23 ng/mouse, linoleic acid: 4489 +/- 179 ng/mouse) and declined to saline control levels by 8 h. PLA2 activity was significantly increased 5 to 15 min after zymosan injection. Maximal levels of PLA2 activity occurred 15 to 30 min after zymosan injection (31.8 +/- 9.1 nmol phospholipid/mg protein/h) and then decreased by 30% through 24 h. Neither the appearance of UnFA nor PLA2 activity correlated with cellular influx, but both were coincident with plasma exudation at 5 to 15 min after zymosan. However, maximal exudation occurred 1 to 2 h post zymosan injection similar to that seen with the UnFA but not PLA2. These latter results suggest that a significant portion of the UnFA found in the peritoneal cavity of zymosan-injected mice originates from the plasma. PLA2 activity at the early time points (5 to 15 min) may also contribute to the levels of UnFA via hydrolysis of tissue and/or cellular phospholipids.
Lundy
S R
SR
E. I. du Pont de Nemours & Co., Pharmaceuticals Research and Development Division, Medical Products Department, Wilmington, DE 19880-0400.
Dowling
R L
RL
Stevens
T M
TM
Kerr
J S
JS
Mackin
W M
WM
Gans
K R
KR
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001202:Ascitic Fluid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015777:Eicosanoids / Q000378:metabolism*; D005122:Exudates and Transudates / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010538:Peritonitis / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011863:Radioimmunoassay; D013997:Time Factors; D015054:Zymosan
D001095:Arachidonic Acids; D015777:Eicosanoids; D016718:Arachidonic Acid; D015054:Zymosan; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2