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Abstract
To examine the potential role of lipoxygenase products in the pathophysiology observed
after experimental tumor implantation, we examined the generation of leukotrienes
(LTs) and hydroxyeicosatetraenoic acids (HETEs) in peritoneal macrophages. ![Math Eq]()
mice were given subcutaneous inoculations of B16 melanoma cells, and peritoneal macrophages
were isolated various days after the inoculation. Macrophages were incubated for 1
h at 37°C in serum-free RPMI1640 containing 10 μM calcium ionophore A23187, 10 μM
exogenous arachidonic acid (AA), 5 mM cysteine hydrochloride and 1 mM reduced glutathione.
LTs and HETEs were separately extracted, passed through Sep-Pak cartridges, then identified
and quantitated with a HPLC system using UV absorbance. The B16 melanoma-cell-treated/untreated
macrophages were found to produced substantial amounts of 15-HETE, 12-HETE and 5-HETE
and LTC4 by enzymatic mechanisms. Thus, when determined under various conditions, the production
of HETEs was dependent on substrate-concentration, incubation-time and cell-number.
The production of LTC4 was dependent on incubation-time and cell number but not substrate-concentration,
indicating utilization of endogenous AA stores. Of these products, 12-HETE and LTC4 showed a significant increase on the fourth day after the tumor cell inoculation
and returned to the control level by the 11th day after the same treatment. These
results suggest that in vivo tumor cell implantation may induce a transient increase
of 12-HETE and LTC4 production in macrophages.
mice were given subcutaneous inoculations of B16 melanoma cells, and peritoneal macrophages
were isolated various days after the inoculation. Macrophages were incubated for 1
h at 37°C in serum-free RPMI1640 containing 10 μM calcium ionophore A23187, 10 μM
exogenous arachidonic acid (AA), 5 mM cysteine hydrochloride and 1 mM reduced glutathione.
LTs and HETEs were separately extracted, passed through Sep-Pak cartridges, then identified
and quantitated with a HPLC system using UV absorbance. The B16 melanoma-cell-treated/untreated
macrophages were found to produced substantial amounts of 15-HETE, 12-HETE and 5-HETE
and LTC4 by enzymatic mechanisms. Thus, when determined under various conditions, the production
of HETEs was dependent on substrate-concentration, incubation-time and cell-number.
The production of LTC4 was dependent on incubation-time and cell number but not substrate-concentration,
indicating utilization of endogenous AA stores. Of these products, 12-HETE and LTC4 showed a significant increase on the fourth day after the tumor cell inoculation
and returned to the control level by the 11th day after the same treatment. These
results suggest that in vivo tumor cell implantation may induce a transient increase
of 12-HETE and LTC4 production in macrophages.To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
July 3,
1991
Received:
May 18,
1991
Identification
Copyright
© 1991 Published by Elsevier Inc.
