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Enhanced Activity of Murine Peritoneal Cells after Aclacinomycin Injection: Characteristics of the Enhanced Respiratory Burst

Institut de Cancérologie et d'Immunogénétique (Université Paris-Sud, Centre National de la Recherche Scientifique UA 04-1163, Association pour la Recherche contre le Cancer and Association Cl.-Bernard), Hôpital Paul-Brousse, 14, av. P. V. Couturier, 94800-Villejuif [A. B-C., J. C., S. O-A.], and Unité 25, Institut National de la Santé et de la Recherche Médicale, Hôpital Necker, 75015-Paris [F. H-D.], France

After the i.p. injection into normal mice, of 4 mg/kg of aclacinomycin (ACM), a dose which prolongs the survival of tumor-bearing mice, the zymosan-elicited chemoluminescence (CL) of the peritoneal cells (PC) is greater than that of control cells. The volume in which the drug is administered plays an important role in the intensity of the response. ACM also stimulated the CL of PC from tumor-bearing mice. It is known that CL can also be elicited by soluble stimuli such as 4ß-phorbol-12-myristate-13-acetate or Ca²⁺ ionophore A 23187, which, however, act in different ways. The response of ACM cells to these stimuli is also greater than in control cells. The enhanced CL of ACM-treated cells can be inhibited by incubating in vitro the zymosan-triggered PC with superoxide dismutase (300 units/ml) and catalase (2750 units/ml), but not with ethanol (20 µM) or potassium cyanide (100 µM). This indicates the participation of O₂^- and H₂O₂ in the CL of ACM-treated cells, whereas mitochondrial respiration does not appear to be involved.

Furthermore, the following facts suggest the participation of arachidonic acid metabolism in the control of CL: (a) the in vitro addition of nordihydroguaiaretic acid (7 x 10^-6 M) and indomethacin (10^-3 M) inhibits the CL, while indomethacin (10^-6 M) has the opposite effect; (b) the PC from normal or ACM-treated mice when stimulated with zymosan secrete high amounts of prostaglandin (PG); (c) treated cells secrete the same amounts of PGE₂ and 6-keto-PGF₁ but the secretion of PGF₂ and particularly of thromboxane B₂ is greater in treated cells than in control cells and indomethacin (10^-6 M) strongly inhibits PG secretion in all groups; (d) in vitro addition of PGE₂ at a concentration of 10^-6 M has an inhibitory effect on the CL emission of control and of treated cells, but it does not have this effect at lower concentrations (10^-6 M). These data suggest that the lipoxygenase pathway of arachidonic acid metabolism may be involved in the triggering of CL of ACM-treated cells, as well as that of normal cells, whereas products of the cyclooxygenase pathway may act as feedback inhibitors.

¹ To whom requests for reprints should be addressed, at ICIG-Hôpital Paul-Brousse, 14, av. P. V. Couturier, 94800-Villejuif, France.

Received 5/21/87. Revised 1/20/88. Accepted 3/21/88.