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We have investigated the effects of murine interferons on the ability of rat alveolar macrophages (AM) to inhibit the proliferation of the intracellular protozoan Toxoplasma gondii.This activity was determined by measuring suppression of 3H‐uracil uptake into the Toxoplasmaand by microscopic enumeration of the intracellular organisms. Recombinant gamma interferon (rMuIFN‐γ), but not alpha/beta interferon (IFN‐α/β) was able to activate AM for antimicrobial activity in vitro. Maximum activation was achieved by incubation with 50‐200 units/ml rMuIFN‐γ and the activity was lost at one unit/ml. The highest levels of activation were obtained when macrophages were incubated with interferon for 48‐72 h prior to the challenge with Toxoplasmaorganisms. Activation could still be obtained, however, when the interferon was added to the cultures as late as 2 h after the phagocytosis of Toxoplasma.Neither MDP nor low concentrations (1‐1‐ng/ml) of S. typhosalipopolysaccharide (LPS) were able to activate these cells to inhibit the growth of Toxoplasma.Phagocytosis of Toxoplasmaby AM did not result in the release of O2−, in fact the spontaneous release of O2−by these cells was inhibited by Toxoplasma.This inhibition was reversed by preincubation of the cells with rMuIFN‐γ.

Human immunodeficiency virus (HIV), the retrovirus believed to be the cause of acquired immunodeficiency syndrome (AIDS), infects a variety of CD4+cells, including lymphocytes and cells of the monocyte/macrophage lineage. Encoded in the HIV genome are several precursor proteins that must undergo proteolytic cleavage to yield functional proteins. The gagprecursor protein of HIV (p55) is cleaved by a virally encoded aspartate protease (HIV protease). Because cleavage of p55 is required for viral maturation and infectivity, inhibition of HIV protease is an attractive target for therapy designed to block the progression of HIV infection. Inhibitors of HIV protease from a variety of chemical classes have been synthesized and antiviral activity has been demonstrated in lymphocytes and cells from the monocyte/macrophage lineage. A few HIV protease inhibitors have progressed to the clinic and some have shown promise in early trials. There are, however, several important issues that will affect the development of a successful HIV protease inhibitor, including cell and tissue distribution and immunotoxicity. These issues are discussed, with an emphasis on the complexities posed by cells of the monocyte/macrophage lineage. J. Leukoc. Biol.56: 374–380; 1994.

A new histochemical technique is described that permits differentiation of resident from recruited macrophages by staining of paraffin sections of tissues from rats and mice. Resident macrophages are identified by their ability to phagocytose and retain intravenously injected colloidal Prussian blue. New macrophages that emigrate into tissue are identified by phagocytosis of a second colloid, iron dextran. Paraffin sections of formalin‐fixed tissues are sequentially stained for the presence of the two colloids with different chromogens, the endogenous pseudo‐peroxidase activity of colloidal Prussian blue used to catalyze the polymerization of diaminobenzidine and after conversion of iron dextran to Prussian blue, the second colloid used to catalyze the polymerization of tetramethylbenzidine. The staining results in resident macrophages staining brown while newly recruited macrophages stain blue. The studies have shown that colloidal Prussian blue is stable in vivo and neither loses its catalytic activity nor undergoes extensive redistribution. They also show that the technique can be used to measure Kupffer cell recruitment stimulated by complete Freund's adjuvant in rats and tumor‐associated macrophage recruitment in subcutaneous and spontaneous liver metastases in mice.