Effect of bacterial endotoxin on lipoxygenase and cyclo-oxygenase metabolites by rat neutrophils and correlation with cellular functional parameters.
The effect of Salmonella enteritidis endotoxin on in vitro rat neutrophil cyclo-oxygenase and lipoxygenase metabolism, phagocytic activity, superoxide (O2-) generation, and microbicidal activity was investigated. Incubation of polymorphonuclear leukocytes (PMN) with 5, 25, and 50 micrograms of endotoxin significantly enhanced synthesis of immunoreactive (i) leukotriene (LT)C4/D4 and thromboxane (Tx)B2 (P less than 0.001) as compared to control cells. Endotoxin 5 micrograms/ml produced optimal stimulation of the arachidonic acid metabolites. Calcium ionophore, A23187, significantly enhanced iLTC4/D4 and iTxB2 synthesis more than that elicited with endotoxin. Although phagocytic function was not significantly altered by endotoxin, intracellular killing of C. albicans demonstrated enhanced microbicidal activity at 5 micrograms/ml of endotoxin. Superoxide generation was significantly enhanced in neutrophils stimulated with phorbol myristate acetate (PMA). Endotoxin (5 micrograms/ml) further potentiated superoxide generation by these cells when stimulated by PMA. These findings demonstrate that endotoxin directly enhances neutrophil iLTC4/D4 and iTxB2 synthesis. The enhanced arachidonic acid metabolism elicited by endotoxin in these cells parallels increased microbicidal activity and superoxide generation.
Altavilla
D
D
Institute of Medical Microbiology, University of Messina, Italy.
Berlinghieri
M C
MC
Focà
A
A
Cook
J A
JA
D000818:Animals; D000898:Antibiosis / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis; D012477:Salmonella enteritidis; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis
D004731:Endotoxins; D013189:SRS-A; D013481:Superoxides; D013929:Thromboxane B2; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases