Nitric oxide production and mycobacterial growth inhibition by murine alveolar macrophages: the sequence of rIFN-γ stimulation and Mycobacterium bovis BCG infection determines macrophage activation

Hanano, Ralph; Kaufmann, Stefan H. E.

doi:10.1016/0165-2478(94)00193-u

Cited by 26 publications

(19 citation statements)

References 14 publications

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“…In addition, we also examined the effect of lactoferrin on macrophage intracellular control of BCG proliferation. One main mechanism for macrophage control of intracellular BCG involves production of NO [74,75], which can be stimulated by activation with IFN-γ [76]. Also, lactoferrin alone has been shown to increase macrophage NO production [77].…”

Section: Discussionmentioning

confidence: 99%

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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The current vaccine for tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is an attenuated strain of Mycobacterium bovis bacillus Calmette-Guerin (BCG). BCG has proven to be effective in children, however, efficacy wanes in adulthood. Lactoferrin, a natural protein with immunomodulatory properties, is a potential adjuvant candidate to enhance efficacy of BCG. These studies define bovine lactoferrin as an enhancer of the BCG vaccine, functioning in part by modulating macrophage ability to present antigen and stimulate T-cells. BCG-infected bone marrow derived macrophages (BMMs) cultured with bovine lactoferrin increased the number of MHC II + expressing cells. Addition of IFN-γ and lactoferrin to BCG-infected BMMs enhanced MHC II expressiona dna increased the ratio of CD86/CD80. Lactoferrin treated BCG-infected BMMs were able to stimulate an increase in IFN-γ production from presensitized CD3 + splenocytes. Together, these results demonstrate that bovine lactoferrin is capable of modulating BCG-infected macrophages to enhance T-cell stimulation through increased surface expression of antigen presentation and costimulatory molecules, which potentially explains the observed in vivo bovine lactoferrin enhancement of BCG vaccine efficacy to protect against virulent MTB infection.

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Section: Discussionmentioning

confidence: 99%

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Hwang¹,

Kruzel

Actor³

2009

Biochimie

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“…Alternatively or additionally, NO • -resistant parasite isolates could inhibit NO • production by macrophages, or other killing mechanisms such as ROI. Importantly, it has been shown that M. bovis inhibits NO • -mediated killing by murine macrophages [48], as do Cryptococcus neoformans [49], Trypanosoma cruzi [50], as well, as L. (L.) amazonensis infection [51]. Other studies have reported that amastigote surface enzymes can inhibit NO • production and thereby reduce leishmanicidal activity [52,53].…”

Section: Discussionmentioning

confidence: 99%

Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensisto nitric oxide correlates with disease severity in Tegumentary Leishmaniasis

et al. 2007

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“…In mouse models, NO production is essential for control of M. tuberculosis and M. bovis but apparently enhances M. avium infection. 2,18,21 Specifically concerning M. a. ptb, peripheral blood monocytes harvested from experimentally infected calves during the early subclinical period have augmented NO production with M. a. ptb antigen stimulation. 44 In this study, the general lack of iNOS immunoreactivity in the M. a. ptb granulomas corresponds to high bacterial loads, which is contrasted by low bacterial burdens in the M. bovis granulomas, which had higher iNOS expression.…”

Section: Discussionmentioning

confidence: 99%

Inducible Nitric Oxide Synthase Immunoreactivity in the Granulomatous Intestinal Lesions of Naturally Occurring Bovine Johne's Disease

et al. 2005

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Inducible nitric oxide synthase (iNOS) is important in the control of a number of intracellular pathogens, including mycobacteria, and is a marker of classic macrophage activation. In human granulomatous diseases such as leprosy, a spectrum of granulomatous lesions is described, ranging from the tuberculoid to lepromatous types. Tuberculoid granulomas are associated with enhanced iNOS production and improved clinical outcomes over the lepromatous types. The aim of this study is to determine whether an association exists between morphology of bovine Johne's disease granulomas and lesion macrophage effector functions. To accomplish this, we retrospectively evaluated 24 cases of bovine Johne's disease. In each case, we recorded the predominant granuloma morphology and evaluated iNOS immunoreactivity and bacterial burden by acid-fast stains and mycobacterial immunolabeling. The results of this study demonstrate that all cases had granulomas with features most similar to the lepromatous type. This morphology correlated with heavy bacterial burdens demonstrated by acid-fast staining and mycobacterial immunoreactivity. None of the cases had high expression of iNOS in mycobacterial-positive granulomas. When iNOS immunoreactivity was identified, it was usually located near the crypts and was distinct from the granulomatous foci. Inducible nitric oxide synthase (iNOS) plays a crucial role in host defense and is a major killing mechanism within macrophages. iNOS is one of three iso-forms of nitric oxide synthase that generates nitric oxide (NO) from L-arginine. iNOS expression is well described in macrophages and neutrophils; however, it has also been reported in several additional cell types including respiratory and digestive epithelia, cardiac myocytes, and endothelium. 10,16,34,41 Within seconds after formation, NO reacts with water and oxygen to form reactive intermediates including NO 2 , NO 3 , N 2 O 2 , and ON00. These reactive nitrogen intermedi-ates (RNI) are highly unstable and are directly toxic to many microorganisms. iNOS expression and RNI production are important for macrophage killing of a wide range of intracellular pathogens including His-toplasma capsulatum, Toxoplasma gondii, Listeria monocytogenes, Mycobacterium tuberculosis, and Ec-tromelia virus (reviewed in MacMicking et al. 30) iNOS expression is induced by several types of signals. Environmental factors such as hypoxia and bacterial components including lipopolysaccharide and mycobacterial lipoarabinomanins will lead to iNOS expression in macrophages. 23,37 In addition, iNOS is strongly induced by T-helper 1 (Th1)-type cytokines including interferon-(IFN), interleukin 2, and tumor necrosis factor-; therefore, iNOS expression is a marker of Th1-mediated macrophage activation. 15,20 Similar to other species of pathogenic mycobacteria, Mycobacterium avium subspecies paratuberculosis (M. a. ptb) is an intracellular pathogen of macrophages and monocytes. 46 The pathogenesis of M. a. ptb infection at the macrophage level is incompletely understood , wi...

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Nitric oxide production and mycobacterial growth inhibition by murine alveolar macrophages: the sequence of rIFN-γ stimulation and Mycobacterium bovis BCG infection determines macrophage activation

Cited by 26 publications

References 14 publications

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Influence of bovine lactoferrin on expression of presentation molecules on BCG-infected bone marrow derived macrophages

Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensisto nitric oxide correlates with disease severity in Tegumentary Leishmaniasis

Inducible Nitric Oxide Synthase Immunoreactivity in the Granulomatous Intestinal Lesions of Naturally Occurring Bovine Johne's Disease

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