Macrophages In Host Defense Research Articles

Phagocytosis as a defense mechanism against infection with leptospiras

The role of macrophages in host defense was studied in vivo and in vitro. The intravenous administration of silica, an agent reported to selectively inactivate macrophages, increased the sensitivity to leptospiral infection and inhibited bacterial clearance. Active immunization with killed organisms or with leptospiral lipopolysaccharide (L-LPS), and passive immunization with a monoclonal antibody showed powerful protective effects against infection in mice. The effect of immunization decreased in silica-treated mice. These findings were supported by electron microscopic examination and observation of killing by macrophages in vitro.

Effects of antiserum to Trypanosoma cruzi on the uptake and rate of killing of vector-borne, metacyclic forms of the parasite by macrophages

Kierszenbaum F., Lima M. F. and Wirth J. J. 1985. Effects of antiserum to Trypanosoma cruzi on the uptake and rate of killing of vector-borne, metacyclic forms of the parasite by macrophages. International Journal for Parasitology 15: 409–413. The contribution of phagocytic function to host defense against infection with metacyclic forms of Trypanosoma cruzi isolated from insect vectors was investigated in mice passively transferred with anti- T. cruzi serum. The protective effect resulting from the passive transfers was significantly reduced by administration of either silica or cobra venom factor (CVF). A more pronounced curtailment of the protective effect was seen when both silica and CVF were administered to the mice. This effect was greater than that calculated by adding the effects produced by silica and CVF alone. In in vitro experiments, presence of anti- T. cruzi antibodies enhanced the capacity of mouse macrophages to take up the metacyclic organisms and increased the proportion of macrophages associating with the parasites. Increased macrophage-parasite association was also seen when either the flagellates or the macrophages were preincubated with the antiserum. Antibody-treated metacyclic forms of T. cruzi were more rapidly cleared by untreated macrophages than parasites pretreated with normal mouse serum. These results support a role for macrophages in host defense against the form of T. cruzi responsible for natural infections and emphasize the role played by anti- T. cruzi antibodies. The combined effect of the silica and CVF treatments suggests that C activity may contribute to the protective action of antibodies through its opsonic properties, though a concomitant role for C-dependent immune lysis cannot be ruled out. These results highlight the protective role of antibodymediated mechanisms against infection with the form of T. cruzi responsible for natural infections.

In vivo activity of lymphokine-activated macrophages in host defense against neoplasia.

Purified splenic macrophage (M phi) from normal DBA/2J mice and mice bearing P815 tumors were examined for responsiveness to lymphokine (LK) preparations containing high concentrations of IFN-gamma. For both normal and tumor-bearing M phi, LK treatment induced morphologic changes and increased the percentage of Ia+ cells from 35 to 55%. Although neither population exhibited spontaneous cytotoxicity toward P815 targets, LK treatment induced considerable tumoricidal activity in tumor-bearing M phi (32 to 80% lysis) but only minimal activity in normal M phi (8 to 17% lysis). Subcutaneous injection of 1 X 10(6)P815 cells into DBA/2J led to progressive tumor growth and death of 100% of the recipients after 27 +/- 3 days. Injection of a 1:18 mixture of P815 with either LK-activated normal or tumor-bearing M phi caused tumor regression after 10 days, and prolonged life until 43 +/- 4 days with tumor-bearing M phi and 39 +/- 3 days with normal M phi. Untreated normal or tumor-bearing M phi were unable to cause the effect (30 +/- 2 days), and lymphocytes could not be substituted for M phi (25 +/- 3 days). In x-irradiated recipients, no effect of LK-activated M phi could be observed (control = 19 +/- 2 days; LK-activated tumor-bearing M phi = 21 +/- 3 days). In addition, administration of an admixture of LK-treated M phi and x-rayed tumor before challenge with viable P815 enabled the recipient to inhibit tumor growth and caused tumor necrosis with inflammatory cell infiltration of the tumor. These observations suggest that, in part, LK-activated M phi may interact in vivo with host-derived cellular components and enhance the immune reactivity of the host against the tumor.

Functional and biochemical studies of multinucleated giant cells derived from the culture of human monocytes.

We compared phagocytic and metabolic activities of multinucleated giant cells (MGC) and macrophages derived from human monocytes after 9-14 d in culture. Phagocytosis of sheep erythrocytes (E) coated with IgG, of E coated with IgM and complement, and of Candida albicans was comparable in MGC and macrophages. The same percentage of ingested fungi was killed by MGC (24 +/- 4%) and macrophages (21 +/- 5%). Approximately 70% of MGC and macrophages exhibited superoxide-dependent reduction of nitroblue tetrazolium during stimulation. Ia antigen was present on approximately 75% of both cell types. Analysis of cell populations separated by nuclear fluorescence indicated that beta-glucosaminidase, acid phosphatase, and beta-glucuronidase activity per cell was higher in MGC, but specific activity of these enzymes was greater in macrophages. These results suggest that MGC have the capacity to function like macrophages in host defense against infection.

Participation of macrophages in host defense against respiratory viruses

Participation of macrophages in host defense against respiratory viruses

Role of macrophages and interferon in natural resistance to mouse hepatitis virus infection.

Among the many models of experimental viral infections, the mouse hepatitis virus (MHV) model offers a number of advantages for investigation of the host-virus relationship: 1. MHV infection is a naturally occurring infection in the mouse (Rowe et al. 1963); Broderson et al. 1976; Ishida et al. 1978) and thus is not an artificial model. 2. In the case of mouse hepatitis virus type 3 (MHV-3), the natural resistance is observed to various degrees according to the mouse strain considered (Virelizier and Allison 1976), with either full susceptibility, full resistance, or semiresistance being present This provides the opportunity to make correlations with parameters of the immune response in a more precise manner than in other models where only two situations (susceptibility and resistance) are observed. 3. The mouse strains showing variable degrees of susceptibility to MHV-3 (namely, A/J, C3H/He, and C57/BL-6) are well-known inbred strains whose biologic parameters have been thoroughly investigated. 4. MHV infections have been among the first models in which the role of macrophages in host defense have been investigated after the pioneering studies of F. Bang and his colleagues (Bang and Warwick 1960; Shif and Bang 1970). 5. MHV-3 induces a very easily recognizable cytopathic effect in mouse macrophage cultures by fusing infected macrophages into multinucleated giant cells (Malucci 1965). The appearance of this cytopathic effect closely parallels the intensity of viral replication and thus provides a useful tool for in vitro studies in macrophages from different strains of mice (Virelizier and Allison 1976). 6. MHV-3 infection is so far the only Coronavirus model in which the protective role of interferon in vivo has been demonstrated (Virelizier and Gresser 1978). 7. Finally, the modification of immune responsiveness during acute or persistent infections has been investigated (Virelizier et al. 1976). KeywordsInterferon ProductionMouse Hepatitis VirusImmune InterferonKuppfer CellAntiviral RoleThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Production by mixed lymphocyte cultures of a type II interferon able to protect macrophages against virus infection

In supernatants of mixed mouse spleen cell cultures established for 4 days, a species-specific inhibitor of virus replication with a broad antiviral spectrum was found. The inhibitor was destroyed by trypsin, was nondialyzable and acid labile, and was not neutralized by antibody to mouse L cell interferon. This indicates that in mixed lymphocyte cultures a type II interferon is made that has no immunological relationship with "fibroblast" interferon. This leukocyte product was shown to protect mouse hepatitis viruses. It is suggested that lymphocyte interferon may collaborate with macrophages in host defense against viruses, as a mediator of cellular immunity.

Comparative Evaluation of Macrophage Inactivation of Endotoxin

SummaryThe comparative evaluation of the endotoxin-detoxifying capacity of diverse populations of rat macrophages was undertaken in order to define the relative role of macrophages in endotoxemia. Actinomycin D-treated mice were employed in the bioassay of submicrogram amounts of endotoxin. Sonicate preparations of rat pulmonary alveolar, peritoneal, hepatic, and splenic macrophages were found to possess significant endotoxin-detoxifying activity. Kupffer cells manifested the greatest activity. In contrast, liver parenchymal cell sonicates did not detoxify endotoxin. The demonstrated endotoxin-detoxifying capacity of macrophages further accept the protective role of macrophages in host defense against endotoxins.