Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi

Abstract

Recombinant murine gamma-interferon (IFN) and supernatants from concanavalin A (ConA)-stimulated spleen cells were tested for their ability to activate resident peritoneal macrophages (M+) for fungicidal activity. M4 monolayers pulsed overnight with IFN exhibited significantly enhanced fungicidal activity against Candida albicans (44 ± 12 versus 0.0%) and Blastomyces dermatitidis (34 ± 1 versus 3 ± 3%). The effect of IFN was dose dependent; however, less IFN (10 U/ml) was required to activate M4 to kill phagocytizable C. albicans than to kill nonphagocytizable B. dermatitidis (1,000 U/mI). ConA-stimulated spleen cell supernatants were also able to activate M4 for fungicidal activity against both fungi. The capacity of ConA-stimulated spleen cell supernatants to activate M4 for fungicidal activity was neutralized in the presence of antibody to murine IFN. ConA-treated monolayers acquired the ability to kill C. albicans, but not B. dermnatitidis, which was shown to be associated with residual (10%) lymphocytes in the monolayers. Lipopolysaccharide (0.001 to 10 ,ug/ml) failed to consistently activate M4 for fungicidal activity. These data show that IFN can exert an immunoregulatory role on M4 defense against these fungal pathogens.

Biological properties in vitro of a combination of recombinant murine interleukin‐3 and granulocyte‐macrophage colony‐stimulating factor

“…It is likely that rGM-CSF activates one or more of these metabolic pathways in macrophages, thereby contributing to the increased anti-fungal action of the cells. Our findings are in line with those of Brumer et a1 (23) who have shown that gamma-interferon activates murine macrophages to kill CA.…”

Antifungal mechanisms of activated murine bronchoalveolar or peritoneal macrophages for Histoplasma capsulatum

“…Resident PM were obtained from peritoneal cells as previously described [17]. Briefly, peritoneal cells (2 5 x 10*/ml CTCM) were plated 01 ml per microtest plate well, incubated for 2h at 37°C in 5% CO2-95% air, and non-adherent cells removed by washing.…”

“…Briefly, peritoneal cells (2 5 x 10*/ml CTCM) were plated 01 ml per microtest plate well, incubated for 2h at 37°C in 5% CO2-95% air, and non-adherent cells removed by washing. Of plated cells, 50% were adherent, of which 90% were non-specific esterase-positive [17].…”

A novel immunosuppressive pathway involving peroxynitrate‐mediated nitration of platelet antigens within antigen‐presenting cells

“…14,15 When interferon is present, iNOS is significantly activated and generates large quantities of NO, and because of the high affinity of NO with superoxide, the ONOOpathway may be preferentially activated. [36][37][38] When NO reacts spontaneously with superoxide to form ONOO -, the latter is very efficient at nitrating and nitrosylating tyrosine (tyr-NO2) and cysteine (cys-SNO) residues, respectively. 23,39 When PLTs were exposed to SIN-1 treatment in vitro, the NO, ONOO -, and superoxide produced caused significant tyrosine nitration of several PLT proteins to be detected and the nitration process did not destroy epitopes for PLT antibody binding, suggesting that the immunogenic epitopes on PLTs are not destroyed by nitration (Fig.…”