| Abstrakt: |
The current results provide direct evidence for a role of tissue macrophages (Mφ) in natural immunity and support the use of immunomodulators to enhance antiviral resistance in immunocompromised individuals. In this study, macrophages (Mφ) in the spleen and liver were eliminated by intravenous (i.v.) injection of the drug dichloromethylene diphosphonate (DMDP) encapsulated in liposomes. The effect of this depletion system on peritoneal Mφ, peripheral blood leukocytes, splenic natural killer (NK) activity, and natural and immunomodulator‐induced host resistance was then assessed. Barrier‐maintained CD‐1 female mice were inoculated i.v. either with DMDP liposomes, free liposomes (containing no DMDP), or saline on day ‐2 or on days ‐3 and ‐1 before cell population analysis or infection. Single or double treatment with DMDP liposomes had no effect on peritoneal Mφ as indicated by no changes in total number, differential counts, or ectoenzyme patterns. Double treatment with DMDP liposomes caused a marked leukocytosis in blood, primarily of lymphocytes and polymorphonuclear leukocytes (PMN), and a transient depression of spontaneous and interferon‐inducible splenic NK activity. The effects on host resistance to i.v. infection with Listeria monocytogenesor herpes simplex virus type 2 (HSV‐2) indicated that i.v. treatment with DMDP liposomes significantly reduced natural resistance to these microorganisms as evidenced by increased mortality and decreased median survival time. When DMDP liposomes‐treated mice were given the immunomodulator maleic anhydride divinyl ether copolymer (MVE‐2) intraperitoneally the day before infection with HSV‐2, the immunosuppressive effect of DMDP liposome treatment was significantly reversed. |
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