Leukotriene C4 is an essential 5-lipoxygenase intermediate in A23187-induced macrophage cytostatic activity against P815 tumor cells.

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) 2:1 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.

• Authors: J A van Hilten, S Ben Efraim, F J Zijlstra, I L Bonta
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) Vol. 39 Issue 4 Pg. 283-90 (Apr 1990) ISSN: 0952-3278 [Print] Scotland
• PMID: 2112758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media
• SRS-A
• Calcimycin
• Arachidonate Lipoxygenases
• Arachidonate 5-Lipoxygenase
• Thymidine

Topics

• Animals
• Arachidonate 5-Lipoxygenase (metabolism)
• Arachidonate Lipoxygenases (metabolism)
• Calcimycin (pharmacology)
• Cell Division
• Culture Media
• Cytosol (metabolism)
• Female
• Macrophage Activation
• Macrophages (metabolism, physiology)
• Mice
• Mice, Inbred BALB C
• SRS-A (metabolism)
• Thymidine (metabolism)
• Tumor Cells, Cultured (cytology)