Cyclophosphamide modulates arachidonic acid metabolism by peritoneal macrophages.
The treatment of mice with a single dose of cyclophosphamide (Cy) (200 mg/kg) enhanced the chemiluminescence (CL) response of peritoneal macrophages (PM) triggered with opsonized zymosan (OpZ). The enhanced CL response could not be attributed to the stimulation of the cyanide-insensitive respiratory burst, since neither superoxide anion release nor immune complex-triggered cytotoxicity, an oxygen-dependent lytic mechanism, were increased in Cy-PM. Then, products of the oxidative metabolism of arachidonic acid were measured. It was found that Cy-PM exhibited increased release of prostaglandin E2 and leukotriene C4 in response to OpZ when compared with resident PM. In contrast, similar levels of thromboxane B2 production were observed in both populations. The activation of macrophage arachidonic acid metabolism reported here may contribute to the immunomodulating action of Cy.
Giordano
M
M
Instituto de Investigaciones Hematológicas (IIHEMA), Academia Nacional de Medicina, Buenos Aires, Argentina.
Geffner
J R
JR
Prat
A
A
Palermo
M S
MS
Serebrinsky
G P
GP
Isturiz
M A
MA
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003520:Cyclophosphamide / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D013189:SRS-A; D016718:Arachidonic Acid; D013929:Thromboxane B2; D003520:Cyclophosphamide; D015232:Dinoprostone; D010100:Oxygen