Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis

Beaman, L; Benjamini, E.; Pappagianis, Demosthenes

doi:10.1128/iai.39.3.1201-1207.1983

Cited by 81 publications

(50 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, activation was not enhanced more by longer periods of exposure before coculture, e.g., 2 or 3 h (data not shown). This contrasts sharply with activation of peritoneal macrophages by supernatants, in which longer periods of exposure (12 h or more) were required for optimal results (2,4,10,26). The significance of these differences in time required for activation by lymphokines is not clear, but they could reflect basic differences in the mechanisms involved or different durations of responsiveness and functional ability of these cell types in in vitro cultivation, or both.…”

Section: Wkcmentioning

confidence: 96%

“…Undiluted or concentrated supernatants were dialyzed at 4°C against 10 volumes of CTCM for 48 h (5 volumes for 24 h and another fresh 5 volumes for 24 h). For these dialysis studies, Spectra/Por 2 tubing with a molecular weight cutoff of 12,000 to 14,000 (Spectrum Medical Indus- (4 h) to 20 x 106 (72 h) per mouse; however, the yield of pellet-1 cells from metrizamide gradients was highest (39%) when PEC were harvested 24 h after treatment ( Fig. 1).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Activation of murine polymorphonuclear neutrophils for fungicidal activity with supernatants from antigen-stimulated immune spleen cell cultures

Brummer¹,

Stevens²

1984

Infect Immun

View full text Add to dashboard Cite

An in vitro model of in vivo immunological activation of murine polymorphonuclear neutrophils (PMN) was developed. Culture supernatants of spleen cells from Blastomyces dermatitidis-immunized mice stimulated with B. dermatitidis antigens in vitro were studied. Incubation of the supernatants with thioglycolate-elicited PMN enabled the cells to significantly reduce (31 +/- 6%) B. dermatitidis inoculum CFU. Optimum production of active supernatants occurred after 4 to 6 days of stimulation in vitro and required 200 micrograms of nonviable B. dermatitidis cells per ml. Generation of activity by immune spleen cells was shown to be antigen specific in that stimulation with a heterologous antigen or stimulation of nonimmune spleen cells with B. dermatitidis antigen did not produce active supernatants. The activity in supernatants was dose dependent, nondialyzable (molecular weight greater than or equal to 14,000), and relatively heat labile (80 degrees C, 30 min). Activation of PMN by supernatants for fungicidal activity against B. dermatitidis required only a short incubation period (1 h) followed by a 2-h coculture (challenge) period. Stimulation of normal spleen cells with concanavalin A also resulted in the production of supernatants capable of activating PMN for significant fungicidal activity (31.1 +/- 8.5%). These findings demonstrate for the first time a link between soluble factors produced by antigen stimulation of sensitized lymphoid cells and activation of PMN for enhanced microbicidal activity. Such a process defines an additional immune defense mechanism whereby the immune host may clear specific microorganisms.

show abstract

Section: Wkcmentioning

confidence: 96%

mentioning

confidence: 99%

Activation of murine polymorphonuclear neutrophils for fungicidal activity with supernatants from antigen-stimulated immune spleen cell cultures

Brummer¹,

Stevens²

1984

Infect Immun

View full text Add to dashboard Cite

show abstract

“…2 In contrast, macrophages obtained from mice vaccinated with formalin-killed spherules stained positively with acridine orange and contained endospores with reduced fungal viability in vitro. 3 The inability of macrophages from nonvaccinated mice to kill endospores has been suggested to be at least partly due to the inhibition of lysosomal fusion, which may explain the negative results of acridine orange staining of the phagocytes. The ure mutant strain of Coccidioides is a valuable tool for studies of the effect of pH on host-pathogen interaction during coccidioidomycosis.…”

Section: Induction Of Host Arginase I Production Compromises Host Defmentioning

confidence: 99%

Virulence Mechanisms of Coccidioides

Hung

Xue

Cole

2007

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

Coccidioides is a fungal respiratory pathogen of humans that can cause disease in both immunosuppressed and immunocompetent individuals. We describe here three mechanisms by which the pathogen survives in the hostile host environment: production of a dominant spherule outer wall glycoprotein (SOWgp) that modulates host immune response and results in compromised cell-mediated immunity to coccidioidal infection, depletion of SOWgp presentation on the surface of endospores, which prevents host recognition of the pathogen when the fungal cells are most vulnerable to phagocytic defenses, and induction of elevated production of host arginase I and coccidioidal urease, which contribute to tissue damage at sites of infection. Arginase I competes with inducible nitric oxide synthase (iNOS) in macrophages for the common substrate, L-arginine, and thereby reduces nitric oxide (NO) production and increases the synthesis of host orinithine and urea. Host-derived L-ornithine may promote pathogen growth and proliferation by providing a pool of the monoamine, which could be taken up and used for synthesis of polyamines via metabolic pathways of the parasitic cells. We have shown that high concentrations of Coccidioides- and host-derived urea at infection sites in the presence of urease produced and released by the pathogen, results in secretion of ammonia and contributes to alkalinization of the microenvironment. We propose that ammonia and enzymatically active urease released from spherules during the parasitic cycle of Coccidioides exacerbate the severity of coccidioidal infection by contributing to a compromised immune response to infection and damage of host tissue at foci of infection.

show abstract

“…Cytokines. Spleen cell suspensions from immunized or nonimmunized mice were prepared, and cytokines were produced (2). Spleen cells were purified by density gradient centrifugation over Ficoll-Hypaque (density = 1.077) (Sigma Chemical Co., St. Louis, Mo.)…”

mentioning

confidence: 99%

Fate of conidia of Paracoccidioides brasiliensis after ingestion by resident macrophages or cytokine-treated macrophages

et al. 1992

View full text Add to dashboard Cite

show abstract

Activation of macrophages by lymphokines: enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis

Cited by 81 publications

References 18 publications

Activation of murine polymorphonuclear neutrophils for fungicidal activity with supernatants from antigen-stimulated immune spleen cell cultures

Activation of murine polymorphonuclear neutrophils for fungicidal activity with supernatants from antigen-stimulated immune spleen cell cultures

Virulence Mechanisms of Coccidioides

Fate of conidia of Paracoccidioides brasiliensis after ingestion by resident macrophages or cytokine-treated macrophages

Contact Info

Product

Resources

About