 |
 | Home | Contact Us | FAQ | Search & Site Map | Link to Us |
 | Sign In | Join | Other 45 Sites in Network |
Medical Forum / General / General / August 2005Iron modulates the replication of virulent Mycobacterium bovis
<<snip>> addition of exogenous iron rendered macrophages of both species much more permissive for the replication of M. bovis. <<snip>> Veterinary Immunology and Immunopathology Article in Press, Corrected Proof - Note to users doi:10.1016/j.vetimm.2005.04.010 Copyright © 2005 Elsevier B.V. All rights reserved. Iron modulates the replication of virulent Mycobacterium bovis in resting and activated bovine and possum macrophages Michel Denis, and Bryce M. Buddle AgResearch, Wallaceville Animal Research Centre, PO Box 40063, Upper Hutt, New Zealand Received 23 September 2004; revised 10 February 2005; accepted 13 April 2005. Available online 1 July 2005. Abstract Bovine and possum macrophages were infected in vitro with a virulent strain of Mycobacterium bovis, and mycobacterial replication was measured in the infected macrophages cultured under a variety of conditions. Virulent M. bovis replicated substantially in alveolar possum macrophages as well as in bovine blood monocyte-derived macrophages. Addition of recombinant bovine interferon-gamma (IFN-?) with low concentrations of lipopolysaccharide (LPS) rendered bovine macrophages significantly more resistant to M. bovis replication. Disruption of iron levels in infected macrophages by addition of apotransferrin or bovine lactoferrin blocked replication of M. bovis in both bovine and possum macrophages. On the other hand, addition of exogenous iron, either in the form of iron citrate or iron-saturated transferrin, rendered macrophages of both species much more permissive for the replication of M. bovis. The impact of iron deprivation/loading on the mycobacteriostatic activity of cells was independent of nitric-oxide release, as well as independent of the generation of oxygen radical species in both possum and bovine macrophages. Exogenous iron was shown to reverse the ability of IFN-?/LPS pulsed bovine macrophages to restrict M. bovis replication. When autologous possum lymphocytes from animals vaccinated with M. bovis strain BCG were added to infected macrophages, they rendered the macrophages less permissive for virulent M. bovis replication. Loading the cells with iron prior to this macrophage-lymphocyte interaction, reversed this immune effect induced by sensitized cells. We conclude that, in two important animal species, intracellular iron level plays an important role in M. bovis replication in macrophages, irrespective of their activation status. Keywords: Mycobacterium bovis; Macrophage; Iron; Interferon-gamma; Possums; Cattle Corresponding author. Tel.: +64 4 4922 1594. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking Dude, what's your obsession with iron? It's almost disturbing. Kim <<snip>> addition of exogenous iron rendered macrophages of both species much more permissive for the replication of M. bovis. <<snip>> Veterinary Immunology and Immunopathology Article in Press, Corrected Proof - Note to users doi:10.1016/j.vetimm.2005.04.010 Copyright © 2005 Elsevier B.V. All rights reserved. Iron modulates the replication of virulent Mycobacterium bovis in resting and activated bovine and possum macrophages Michel Denis, and Bryce M. Buddle AgResearch, Wallaceville Animal Research Centre, PO Box 40063, Upper Hutt, New Zealand Received 23 September 2004; revised 10 February 2005; accepted 13 April 2005. Available online 1 July 2005. Abstract Bovine and possum macrophages were infected in vitro with a virulent strain of Mycobacterium bovis, and mycobacterial replication was measured in the infected macrophages cultured under a variety of conditions. Virulent M. bovis replicated substantially in alveolar possum macrophages as well as in bovine blood monocyte-derived macrophages. Addition of recombinant bovine interferon-gamma (IFN-?) with low concentrations of lipopolysaccharide (LPS) rendered bovine macrophages significantly more resistant to M. bovis replication. Disruption of iron levels in infected macrophages by addition of apotransferrin or bovine lactoferrin blocked replication of M. bovis in both bovine and possum macrophages. On the other hand, addition of exogenous iron, either in the form of iron citrate or iron-saturated transferrin, rendered macrophages of both species much more permissive for the replication of M. bovis. The impact of iron deprivation/loading on the mycobacteriostatic activity of cells was independent of nitric-oxide release, as well as independent of the generation of oxygen radical species in both possum and bovine macrophages. Exogenous iron was shown to reverse the ability of IFN-?/LPS pulsed bovine macrophages to restrict M. bovis replication. When autologous possum lymphocytes from animals vaccinated with M. bovis strain BCG were added to infected macrophages, they rendered the macrophages less permissive for virulent M. bovis replication. Loading the cells with iron prior to this macrophage-lymphocyte interaction, reversed this immune effect induced by sensitized cells. We conclude that, in two important animal species, intracellular iron level plays an important role in M. bovis replication in macrophages, irrespective of their activation status. Keywords: Mycobacterium bovis; Macrophage; Iron; Interferon-gamma; Possums; Cattle Corresponding author. Tel.: +64 4 4922 1594. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking Of course .. virulent .. infection .. DOESN'T BELONG .. in medical newsgroups .. Does .. it .. You .. as opposed to .. almost .. ARE .. disturbing .. Heh . heh .. How does it feel to be soooo .. stupid ..? Eh .. Describe .. it .. Heh .. heh .. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking That's right. I am so stupid. And next time we have a mycobacterium infection in the ICU, I'll recommend to the doctor that we try iron chelation instead of rifampin. Cheers Kim > Of course .. virulent .. infection .. DOESN'T BELONG .. in medical > newsgroups .. [quoted text clipped - 22 lines] > DEAD PEOPLE WALKING > http://pages.ivillage.com/ironjustice/deadpeoplewalking You ARE a .. quick .. learner .. I may have been a bit hasty in my assessment of .. your .. intelligence .. BUT .. the 'instead of'.. has me a bit .. worried .. I think as an adjunct TO rifampin .. may be the way to .. go .. Int J Tuberc Lung Dis. 2005 Jan;9(1):2-9. Related Articles, Links Iron overload and tuberculosis: a case for iron chelation therapy. Cronje L, Bornman L. Division of Biochemistry, Department of Chemistry and Biochemistry, University of Johannesburg, Auckland Park, South Africa. Elevated levels of iron impair immune defence mechanisms, and specifically the macrophage function of innate immunity. Iron enhances Mycobacterium tuberculosis infection, M. tuberculosis replication, progression to clinical disease and death from tuberculosis (TB). Chelation of iron in individuals with an excessive iron burden may reduce M. tuberculosis viability and replication, restore host defence mechanisms and could find application in the prevention and treatment strategies in settings where both iron overload and TB are prevalent. The objective of this paper was to summarise recent literature on the role of iron in TB pathogenesis and to examine the potential of iron chelation therapy. The literature confirms a key role for iron in mycobacterial virulence. The ability of chelation to enhance host effector mechanisms and to inhibit replication of various pathogens justifies further studies into iron chelation as a potential additive therapy for TB. Publication Types: Review Review, Tutorial PMID: 15675543 [PubMed - indexed for MEDLINE] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking .. Just in case my original assessment of your intelligence .. may .. have been correct .. watch what you .. feed .. him .. <<snip>> The management of dietary iron can therefore be influential in aiding the outcome of this disease. <<snip>> Tuberculosis (Edinb). 2004;84(1-2):110-30. Related Articles, Links Iron, mycobacteria and tuberculosis. Ratledge C. Department of Biological Sciences, University of Hull, Hull HU6 7RX, UK. c.ratledge@biosci.hull.ac.uk The role of iron in the growth and metabolism of M. tuberculosis and other mycobacteria is discussed in relation to the acquisiton of iron from host sources, such as transferrin, lactoferrin and ferritin, and its subsequent assimilation and utilization by the bacteria. Key components involved in the acquisition of iron (as ferric ion) and its initial transport into the mycobacterial cell are extracellular iron binding agents (siderophores) which, in pathogenic mycobacteria, are the carboxymycobactins and, in saprophytic mycobacteria, are the exochelins. In both cases, iron may be transferred to an intra-envelope, short-term storage molecule, mycobactin. For transport across the cell membrane, a reductase is used which converts FeIII-mycobactin to the FeII form. The ferrous ion, possibly complexed with salicylic acid, is then shuttled across the membrane either for direct incorporation into various porphyrins and apoproteins or, for storage of iron within the bacterial cytoplasm, bacterioferritin. The overall process of iron acquisition and its utilization is under very genetic tight control. The importance of iron in the virulence of mycobacteria is discussed in relationship to the development of tuberculosis. The management of dietary iron can therefore be influential in aiding the outcome of this disease. The role of the old anti-TB compound, p-aminosalicylate (PAS), is discussed in its action as an inhibitor of iron assimilation, together with the prospects of being able to synthesize further selective inhibitors of iron metabolism that may be useful as future chemotherapeutic agents. Publication Types: Review Review, Tutorial PMID: 14670352 [PubMed - indexed for MEDLINE] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking > Dude, what's your obsession with iron? It's almost disturbing. Excess dietary iron, such as occurs with human necrophages, is not healthy. http://www.ecologos.org/iron.htm Laurie >> Dude, what's your obsession with iron? It's almost disturbing. > Excess dietary iron, such as occurs with human necrophages, is not > healthy. > http://www.ecologos.org/iron.htm Whole baby clams (not your father's meat) are very rich in iron. Laurie, You cross-posting B**** What must your life be like to have it consumed by -- Iron. > Laurie, > > You cross-posting B**** > > What must your life be like to have it consumed by -- Iron. Your confusing me with someone else. Poor reading comprehension?? The msg was already cross-posted, not by me. Laurie |
Reply to this Message |
 Sign In
 Join
 My Latest Posts My Monitored Threads My Blog My Photo Gallery My Profile My Homepage Start New Thread Enable EMail Alerts Rate this Thread
|
©2008 Advenet LLC Privacy Policy - Terms of Use
This website includes both content owned or controlled by Advenet as well as content owned or controlled by third parties.