Plasma membrane expression of heat shock protein 60 in vivo in response to infection.
Heat shock protein 60 (hsp60) is constitutively expressed in the mitochondria of eukaryotic cells. However, it has been identified in other subcellular compartments in several disease states and in transformed cells, and it is an immunogenic molecule in various infectious and autoimmune diseases. To better understand the factors that influence expression of hsp60 in normal cells in vivo, we analyzed its cellular and subcellular distribution in mice infected with the intracellular bacterium Listeria monocytogenes. Western blotting of subcellular fractionated spleen cells showed that although endogenous hsp60 was restricted to the mitochondria in noninfected animals, it was associated with the plasma membrane as a result of infection. The low levels of plasma membrane-associated hsp60 seen in the livers in noninfected animals subsequently increased during infection. Plasma membrane hsp60 expression did not correlate with bacterial growth, being most evident during or after bacterial clearance and persisting at 3 weeks postinfection. Using flow cytometry, we determined that Mac-1(+), T-cell receptor gammadelta(+), and B220(+) cells represented the major Hsp60(+) populations in spleens of infected mice. By contrast, B220(+) cells were the predominant hsp60(+) population in livers of infected mice. Of the immune cells analyzed, the kinetic profile of the gammadelta T-cell response most closely matched that of hsp60 expression in both the spleen and liver. Collectively, these findings show that during infection hsp60 can be localized to the plasma membrane of viable cells, particularly antigen-presenting cells, providing a means by which hsp60-reactive lymphocytes seen in various infectious disease and autoimmune disorders may be generated and maintained.
Belles
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Department of Clinical Studies, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6010, USA.
Kuhl
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Nosheny
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Carding
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D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018834:Chaperonin 60 / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013154:Spleen / Q000378:metabolism
D018834:Chaperonin 60; D016692:Receptors, Antigen, T-Cell, gamma-delta