Other works on Macrophage Activation

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Inhibited Growth of a Reticulum Cell Sarcoma (M5076) Induced in Vitro and in Vivo by Macrophage-activating Agents by J. E. Talmadge and I. R. Hart. CANCER RESEARCH 44, 2446-2451, June 1984].

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Depression of macrophages in mice drinking hyperchlorinated water.
Isaiah J. Fidler / Nature 270, 735 - 736 (22 December 1977); doi:10.1038/270735a0

We have encountered a problem with the collection and in vitro activation of peritoneal exudate macrophages (PEM) from mice, which we can now associate with high levels of chlorine in the drinking water. Historically the chlorination of drinking water in colonies of experimental rodents was carried out in order to avoid the so-called early death syndrome in lethally irradiated animals, which is due to pathogenic enteric bacteria such as Pseudomonas. The recommended level of chlorine necessary to achieve this goal is 12−16 parts per million (p.p.m.)1. Because of an unusually high incidence of Pseudomonas within a few breeding units of our animal facility, the chlorination level of the drinking water was increased to 25−30 p.p.m. We found that this hyperchlorination had an adverse effect on an important host defense mechanism, that is the macrophage system, whose primary function is to eliminate microbial pathogens2,3 and neoplasms3,4.

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Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines
IJ Fidler / Science 27 June 1980: Vol. 208. no. 4451, pp. 1469 - 1471
Abstract: Mice of two different strains were injected subcutaneously with spontaneously metastasizing syngeneic melanomas. After 4 to 6 weeks, the local tumors were removed and, 3 days after surgery, treatment of the metastases was initiated. The treatment consisted of intravenous injections of liposomes containing lymphokines or control supernatant fluids. Liposomes were injected twice weekly for 3 weeks, and the mice were killed 2 weeks later. Seventy-three percent of the mice injected with liposomes containing lymphokines were free of metastases, whereas only 10 percent of the mice treated with control liposomes were tumor-free. These experiments suggest that this form of therapy may provide a valuable addition to the more conventional approaches to the eradication of cancer metastases.

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Macrophage Activation by Poly(maleic acid-alt-2-cyclohexyl-1,3-dioxap-5-ene) Encapsulated in Polysaccharide-Coated Liposomes
Toshinori Sato, Kazuyuki Kojima, Taka-Aki Ihda, Junzo Sunamoto, Raphael M. Ottenbrite
Journal of Bioactive and Compatible Polymers, Vol. 1, No. 4, 448-460 (1986)

An increase in the efficiency of macrophage activation has been tried by encapsulating potent polyanionic polymer immunomodulators into polysac charide-coated liposomes. For this purpose, several alternating copolymers of maleic acid (MA) and itaconic acid (IT) with 2-cyclohexyl-1,3-dioxap-5-ene (CDA), styrene (ST), and other monomers have been synthesized and frac tionated.

First, the interaction between the liposomes and polyanionic polymers was investigated. As a result, poly(maleic acid-alt-2-cyclohexyl-1,3-dioxap-5-ene) (MA-CDA) was found to be the best candidate for encapsulating in the liposome while poly(itaconic acid-alt-styrene)(IA-ST) strongly perturbed these vesicles.

Based on these results, MA-CDA was encapsulated in the mannan derivative-coated liposomes and the macrophage activation activity was evaluated from the superoxide production of the activated macrophages in vivo. Compared with the administration of free MA-CDA, the maximum in the superoxide production appeared faster (2 h after injection) and the activity was significantly increased.

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Human monocytes activated by immunomodulators in liposomes lyse herpesvirus-infected but not normal cells.

WC Koff, IJ Fidler, SD Showalter, MK Chakrabarty, B Hampar, LM Ceccorulli, and ES Kleinerman /
Science 1 June 1984: Vol. 224. no. 4652, pp. 1007 - 1009

Highly purified peripheral blood monocytes from normal human donors were activated in vitro by incubation with liposomes containing immunomodulators such as recombinant human gamma interferon, human lymphokines, or muramyl dipeptide. The ability of liposomes containing immunomodulators to activate monocytes to a cytotoxic state capable of discriminating between virus-infected and uninfected cells was shown by activated monocytes recognizing and destroying herpes simplex virus type 2-infected cells while leaving uninfected cells unharmed .

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