Trypanosoma cruzi: in vitro induction of macrophage microbicidal activity.

Nogueira, N; Cohn, Zanvil A.

doi:10.1084/jem.148.1.288

Cited by 156 publications

(80 citation statements)

References 20 publications

(17 reference statements)

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“…• ulated by SNa; under these conditions however, parasite killing was delayed by =24 h, a finding already reported by Nogueira and Cohn (5). For convenience, only starch-induced cells were used in the following experiments.…”

Section: 'supporting

confidence: 48%

Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.

Büchmuller¹,

Mauël²

1979

The Journal of Experimental Medicine

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Activation of mouse peritoneal exudate macrophages, as evidenced by destruction of the intracellular protozoan parasite Leishmania enriettii, was obtained by incubation with supernates from concanavalin A (Con A)-stimulated syngeneic spleen cells. Parasites were not destroyed in macrophages exposed to control media. Supernate-induced activation was independent of the presence of Con A. The activating principle (macrophage activating factor, or MAF) was produced by Con A-stimulated lymphocytes in presence or absence of serum. In absence of serum, MAF synthesis was highest at Con A concentrations far below those required in serum-containing media. MAF production was reduced at Con A concentrations of 10 microgram/ml or above, probably a result of toxicity of the lectin for lymphocytes. MAF was detectable after 24 h of lymphocyte stimulation and increased up to 72 h; production appeared to be independent of DNA synthesis. Serum-free MAF was inactive when tested as such on macrophages. Full activity could be restored by addition of nanogram amounts of endotoxin or of FCS before assay. Endotoxin also considerably potentiated MAF activity in serum-containing supernates. Full intracellular parasite destruction was observed after contact of macrophages with MAF for 20 h. The continuous presence of MAF was not necessary for activation; a 10-h pulse was sufficient to induce macrophages to destroy all intracellular microorganisms within the next 38 h.

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Section: 'supporting

confidence: 48%

Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.

Büchmuller¹,

Mauël²

1979

The Journal of Experimental Medicine

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“…When a lymphokine-rich conditioned medium was produced by spleen cells from infected mice and applied to otherwise nonresistant phagocytes in vitro, the group induced sterilizing resistance and other parameters of macrophage activation (Fig. 8) (124,131). They made similar findings with human monocytes (207).…”

Section: Macrophage Activation: Antimicrobial and Antitumor Activitiessupporting

confidence: 66%

Zanvil Alexander Cohn 1926-1993.

Steinman¹,

Moberg²

1994

The Journal of Experimental Medicine

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SummaryZanvil Alexander Cohn, an editor of this Journal since 1973, died suddenly on June 28, 1993. Cohn is best known as the father of the current era of macrophage biology. Many of his scientific accomplishments are recounted here, beginning with seminal studies on the granules of phagocytes that were performed with his close colleague and former editor of thisJournaI, James Hirsch. Cohn and Hirsch identified the granules as lysosomes that discharged their contents of digestive enzymes into vacuoles containing phagocytosed microbes. These findings were part of the formative era of cell biology and initiated the modern study of endocytosis and cell-mediated resistance to infection. Cohn further explored the endocytic apparatus in pioneering studies of the mouse peritoneal macrophage in culture. He described vesicular inputs from the cell surface and Golgi apparatus and documented the thoroughness of substrate digestion within lysosomal vacuoles that would only permit the egress of monosaccharides and amino acids. These discoveries created a vigorous environment for graduate students, postdoctoral fellows, and junior and visiting faculty. Some of the major findings that emerged from Cohn's collaborations included the radioiodination of the plasma membrane for studies of composition and turnover; membrane recycling during endocytosis; the origin of the mononuclear phagocyte system in situ; the discovery of the dendritic cell system of antigen-presenting cells; the macrophage as a secretory cell, including the release of proteases and large amounts of prostaglandins and leukotrienes; several defined parameters of macrophage activation, especially the ability of T cell-derived lymphokines to enhance killing of tumor cells and intracellular protozoa; the granule discharge mechanism whereby cytotoxic lymphocytes release the pore-forming protein perforin; the signaling of macrophages via myristoylated substrates of protein kinase C; and a tissue culture model in which monocytes emigrate across tight endothelial junctions. In 1983, Cohn turned to a long-standing goal of exploring host resistance directly in humans. He studied leprosy, focusing on the disease site, the parasitized macrophages of the skin. He injected recombinant lymphokines into the skin and found that these molecules elicited several cell-mediated responses. Seeing this potential to enhance host defense in patients, Cohn was extending his clinical studies to AIDS and tuberculosis. Zanvil Cohn was a consummate physician-scientist who nurtured the relationship between cell biology and infectious disease. He guided with a warm but incisive manner the careers of many individuals. He was deeply committed to several institutions of biomedical research; to medicine in the developing world; to The Rockefeller University, especially its programs for graduate study and patient-oriented research;and to the energy and spirit of this Journal.

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“…It is well established that macrophages play a major role in resistance to T. cruzi infection [12,19,20]. Activated macrophages are highly competent to produce anti-microbial agents and kill T. cruzi, while unactivated macrophages are successfully parasitized [7].…”

Section: Immunization With Recombinant Pfr Antigens Produce Cd4 + T Cmentioning

confidence: 99%

Immunization with recombinant paraflagellar rod protein induces protective immunity against Trypanosoma cruzi infection

Luhrs

Fouts

Manning

2003

Vaccine

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In the present study, we have produced recombinant paraflagellar rod proteins (PFR) and report their use for successful vaccination of mice against Trypanosoma cruzi. This protection is associated with a highly polarized type 1 cytokine production profile. Additionally, we have analyzed the gene sequence encoding PFR-2 to determine the degree of conservation among seven highly diverse strains of T. cruzi, and found it to be highly conserved. The results presented here indicate that the PFR antigens are highly conserved, and immunization with rPFR-1, PFR-2, or an equimolar mix of the PFR-1, -2, and -3 proteins provides protective immunity against Trypanosoma cruzi.

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Trypanosoma cruzi: in vitro induction of macrophage microbicidal activity.

Cited by 156 publications

References 20 publications

Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.

Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.

Zanvil Alexander Cohn 1926-1993.

Immunization with recombinant paraflagellar rod protein induces protective immunity against Trypanosoma cruzi infection

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