Leukotriene C4 is an essential 5-lipoxygenase intermediate in A23187-induced macrophage cytostatic activity against P815 tumor cells.
Prostaglandins Leukot Essent Fatty Acids
; 39(4): 283-90, 1990 Apr.
Article
em En
| MEDLINE
| ID: mdl-2112758
ABSTRACT
Resident peritoneal macrophages incubated with 3.5 x 10(-7) M Calcium ionophore A23187 in tumor cell growth medium (TGM) release large amounts of leukotriene (LT)E4 and an unidentified 5-lipoxygenase product, whereas A23187-stimulated macrophages produce in serum free medium LTD4, predominately. LTC4 and 3H-LTC4 incubated for 20 min at 37 degree C in serum containing TGM, convert into LTE4 and 3H-LTE4, respectively. Thus, LTC4 released from A23187-stimulated macrophages is an intermediate in TGM which rapidly converts into LTE4, probably because of the presence of gamma-glutamyl transpeptidase and cystenylglycinase in TGM. Macrophages express antitumor cytostatic activity towards P815 cells (49-53%) in a cocultured ratio (macrophage tumor cell) 21 when stimulated with 3.5 x 10(-7) M A23187 in TGM. The 5-lipoxygenase inhibitor AA861 reverses the cytostatic activity by 42-58% and it inhibits also the formation of A23187-induced 5-lipoxygenase products from macrophages. Restoration of 38% macrophage- antitumor cytostatic activity by exogenous LTC4 (10(-8) M) indicates that LTC4 is an essential 5-lipoxygenase intermediate in the pathway of required signals underlying A23187-induced macrophage antitumor cytostatic activity. Macrophages not stimulated by A23187 do not express cytostatic activity in the presence of LTC4. This implies that besides LTC4, increased cytosolic [Ca2+] is required for A23187 induction of macrophage cytostatic activity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Araquidonato 5-Lipoxigenase
/
Araquidonato Lipoxigenases
/
Células Tumorais Cultivadas
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SRS-A
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Calcimicina
/
Macrófagos
Limite:
Animals
Idioma:
En
Revista:
Prostaglandins Leukot Essent Fatty Acids
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
1990
Tipo de documento:
Article
País de afiliação:
Holanda