Abstract:
:Rickettsia rickettsii infection of endothelial cells is manifested in very distinctive changes in cell morphology, consisting of extensive dilatation of the membranes of the endoplasmic reticulum and outer nuclear envelope and blebbing of the plasma membrane, as seen by transmission electron microscopy (D. J. Silverman, Infect. Immun. 44:545-553, 1984). These changes in cellular architecture are thought to be due to oxidant-mediated cell injury, since their occurrence correlates with dramatic alterations in cellular metabolism, particularly with regard to antioxidant systems. In this study, it was shown that R. rickettsii infection of human umbilical vein endothelial cells resulted in a significant depletion of intracellular reduced glutathione (thiol) content at 72 and 96 h and decreased glutathione peroxidase activity at 72 h postinfection. Infected cells displayed a dramatic increase in the concentration of intracellular peroxides by 72 h. Supplementation of the cell culture medium with 100, 200, or 500 microM alpha-lipoic acid, a metabolic antioxidant, after inoculation with R. rickettsii restored the intracellular levels of thiols and glutathione peroxidase and reduced the intracellular peroxide levels in infected cells. These effects were dose dependent. Treated infected monolayers maintained better viability at 96 h after inoculation with R. rickettsii than did untreated infected cells. Moreover, supplementation of the cell culture medium with 100 microM alpha-lipoic acid for 72 h after infection prevented the occurrence of morphological changes in the infected cells. The presence of 100 or 200 microM alpha-lipoic acid did not influence rickettsial growth in endothelial cells, nor did it affect the ability of R. rickettsii to form lytic plaques in Vero cells. Treatment with 500 microM alpha-lipoic acid decreased by 50% both the number and size of lytic plaques in Vero cells, and it also decreased the recovery of viable rickettsiae from endothelial cells. However, under all treatment conditions, a significant number of rickettsiae could be detected microscopically. Furthermore, the rickettsiae apparently retained their capacity for intracellular movement, since they possessed long polymerized actin tails after 72 and 96 h of treatment regardless of the concentration of alpha-lipoic acid used. Since alpha-lipoic acid does not seem to exhibit direct antirickettsial activity except with long-term exposure at very high concentrations, the mechanism of its protective activity for endothelial cells infected with rickettsiae may involve complex changes in cellular metabolism that only indirectly affect rickettsiae.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Eremeeva ME,Silverman DJdoi
10.1128/IAI.66.5.2290-2299.1998subject
Has Abstractpub_date
1998-05-01 00:00:00pages
2290-9issue
5eissn
0019-9567issn
1098-5522journal_volume
66pub_type
杂志文章abstract::The cellular origins of type I and type II interferons released into the circulation of mice with delayed hypersensitivity were investigated. We determined the effect of treatment with various immunosuppressive agents, including cyclophosphamide, cycloheximide, antithymocyte serum, and whole-body X-irradiation, on the...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.18.2.283-290.1977
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journal_title:Infection and immunity
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doi:10.1128/IAI.05580-11
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.42.2.763-770.1983
更新日期:1983-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/iai.70.12.7153-7155.2002
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.43.1.139-142.1984
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pub_type: 杂志文章
doi:10.1128/IAI.00925-15
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.11.4893-4899.1994
更新日期:1994-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.8.2.215-221.1973
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.40.1.166-171.1983
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.2.638-644.1991
更新日期:1991-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.4.1538-1543.1993
更新日期:1993-04-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00027-14
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.45.2.511-517.1984
更新日期:1984-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.17.1.117-120.1977
更新日期:1977-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00417-20
更新日期:2020-12-15 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.3.3.488-493.1971
更新日期:1971-03-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.7.5.725-730.1973
更新日期:1973-05-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.37.1.60-63.1982
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journal_title:Infection and immunity
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doi:10.1128/IAI.26.2.402-407.1979
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.9.5.934-938.1974
更新日期:1974-05-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.69.3.1729-1738.2001
更新日期:2001-03-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01817-14
更新日期:2014-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.12.6.1415-1425.1975
更新日期:1975-12-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.11.2734-2740.1987
更新日期:1987-11-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.68.7.4135-4144.2000
更新日期:2000-07-01 00:00:00
abstract::The 9.5-kilobase plasmid of Yersinia pestis determines plasminogen activator, coagulase, pesticin, and pesticin immunity activities. We have mapped and cloned the loci encoding these activities and demonstrated that both plasminogen activator and coagulase were determined by the same gene, designated pla. The primary ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.10.2743-2748.1988
更新日期:1988-10-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.57.1.231-234.1989
更新日期:1989-01-01 00:00:00
abstract::Human genital Chlamydia infection is a major public health concern due to the serious reproductive system complications. Chlamydia binds several receptor tyrosine kinases (RTKs) on host cells, including the epidermal growth factor receptor (EGFR), and activates cellular signaling cascades for host invasion, cytoskelet...
journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2020-03-23 00:00:00