Fungicidal mechanisms of activated macrophages: evidence for nonoxidative mechanisms for killing of Blastomyces dermatitidis

Abstract

The mechanism(s) by which lymphokine-activated peritoneal macrophages kill Blastomyces dermatitidis was studied. Resident peritoneal macrophages from BALB/cByJ mice, when treated overnight with lymph node cells plus concanavalin A, supernatants from concanavalin A-stimulated spleen cells, or recombinant gamma interferon, were then able to kill a virulent B. dermatitidis isolate (ATCC 26199) (at levels of 25% ± 4%, 28% ± 8%, and 21% ± 5%, respectively). Killing was not significantly decreased or enhanced in the presence of superoxide dismutase (450 U/ml), catalase (20,000 U/mI), dimethyl sulfoxide (300 mM), or azide (1 mM). Viable B. dermatitidis elicited a brisk oxidative burst and superoxide anion production in activated macrophages as measured by lucigenin-enhanced chemiluminescence, e.g., 104 cpm. However, these responses were not significantly different from those of control macrophages. Luminol-enhanced chemiluminescence responses by activated or control macrophages were meager (-102 cpm). These results indicate that activated macrophages kill B. dermatitidis by a mechanism(s) independent of products of the oxidative burst.

Acquired immunity in experimental murine aspergillosis is mediated by macrophages

“…Activation of macrophages, first described in vivo and then in vitro with lymphokines, has been demonstrated for fungicidal activities against Candida albicans (5,6,8,12), Cryptococcus neoformans (33), Histoplasma capsulatum (47)(48)(49)(50), Blastomyces dermatitidis (8,9), Coccidioides immitis (2-4), and Paracoccidioides brasiliensis (7). Enhanced clearance of the i.v.…”

In vitro study of contact-mediated killing of Candida albicans hyphae by activated murine peritoneal macrophages in a serum-free medium

“…confirmed. Radiolabeling techniques also show that other fungi (5,6,13,16) are damaged by extracellular mechanisms of phagocytes. The propensity of hyphae to clump in suspensions has rendered the routine use of the conventional colony count technique unfeasible for hyphal viability deter- Effect of in vitro cultivation of activated macrophages on the extracellular killing activity against C. albicans hyphae.…”

Cytotoxic reactions of rainbow trout, Salmo gairdneri Richardson, macrophages for larvae of the eye fluke Diplostomum spathaceum (Digenea)

“…This was so in the present study, although the response was not as high as for PMA, which may be due to the fact that the concentration of PMA had been optimized for respiratory burst assays whereas in the case of D. spathaceum only a single concentration of diplostomules was used, approximating to a cell : parasite ratio of 2000 : 1, as used in the previous experiments. Respiratory burst activity may not be the only mechanism involved in parasite killing by macrophages; oxygen-independent factors such as cationic proteins (Segal et al, 1985), proteases (Adams et al, 1980;Malkin et al, 1987;Brummer & Stevens, 1987), cytolytic tumour necrosis factors (Drysdale et al, 1983) and various other factors which have yet to be defined (Scott et al, 1985) may also be important. Whether such factors are involved in the killing of D .…”