| JWissmille 2004-11-10, 4:08 am |
| *Anaplasma = Ehrlichia
http://www.ncbi.nlm.nih.gov/entrez/...db=pubmed&dopt=
Abstract&list_uids=12654818
Infect Immun. 2003 Apr;71(4):1995-2001.
**Anaplasma phagocytophilum reduces neutrophil apoptosis in vivo.
**Scaife H, Woldehiwet Z, Hart CA, Edwards SW.*
School of Biological Sciences, Life Sciences Building, university of
Liverpool, Liverpool L69 3BX, United Kingdom.
Ovine neutrophils spontaneously underwent apoptosis during culture in
vitro, as assessed by morphological changes and exposure of annexin V
binding sites on their cell surfaces. The addition of conditioned medium
from concanavalin A-treated ovine peripheral blood mononuclear cells
(PBMC) could partially protect against this progression into apoptosis,
but dexamethasone and sodium butyrate could not. Actinomycin D
accelerated the rate at which ovine neutrophils underwent apoptosis.
Neutrophils isolated from sheep experimentally infected with Anaplasma
phagocytophilum showed significantly delayed apoptosis during culture ex
vivo, and the addition of conditioned medium from PBMC to these cells
could not delay apoptosis above the protective effects observed after in
vivo infection. The ability of neutrophils from A.
phagocytophilum-infected sheep to activate a respiratory burst was
increased compared to the activity measured in neutrophils from
uninfected sheep, but chemotaxis was decreased in neutrophils from
infected sheep. These data are the first demonstration that in vivo
infection with A. phagocytophilum results in changes in rates of
apoptosis of infected immune cells. This may help explain how these
bacteria replicate in these normally short-lived cells.
PMID: 12654818 [PubMed - indexed for MEDLINE
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http://www.ncbi.nlm.nih.gov/entrez/...db=pubmed&dopt=
Abstract&list_uids=14531890
Cell Microbiol. 2003 Nov;5(11):743-54.
*Invasion and survival strategies of Anaplasma phagocytophilum.*
*Carlyon JA, Fikrig E.*
Section of Rheumatology, Department of Internal Medicine, Yale
University School of Medicine, Room 525A, 300 Cedar Street, New Haven,
CT 06520-8031, USA.
Anaplasma phagocytophilum is an aetiological agent of human granulocytic
ehrlichiosis, an emerging tick-borne zoonosis in the United States and
Europe. This obligate intracellular bacterium is unique in that it
colonizes polymorphonuclear leucocytes (neutrophils). Neutrophils are
key players in innate immunity. These short-lived phagocytes ingest
invading microorganisms and destroy them by various means, which include
fusing the bacteria-containing phagosome with acidic lysosomes as well
as directing toxic oxidative and proteolytic compounds into the
phagosomal lumen. Its tropism for neutrophils indicates that A.
phagocytophilum uses strategies for evading and/or neutralizing these
microbicidal activities. This review focuses on some of the mechanisms
that A. phagocytophilum uses for neutrophil adhesion, surviving within
the hostile intracellular environment of its host neutrophil and for
effectively disseminating to naïve host cells.
Publication Types:
* Review
* Review, Tutorial
PMID: 14531890 [PubMed - indexed for MEDLINE]
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http://www.blackwell-synergy.com/li...822.2004.00427.
x/abs/;jsessionid=eEXXGV5BEGQ7
Cellular Microbiology
doi:10.1111/j.1462-5822.2004.00427.x
Received 29 March, 2004; revised 11 May, 2004; accepted 17 May, 2004.
Department of Veterinary Biosciences, The Ohio State University,
Columbus, OH 43210, USA.
Correspondence E-mail <rikihisa.1@osu.edu>
Anaplasma phagocytophilum/ inhibits human neutrophil apoptosis via
upregulation of /bfl-1/, maintenance of mitochondrial membrane potential
and prevention of caspase 3 activation
Yan Ge^1 Kiyotaka Yoshiie^1+ , Futoshi Kuribayashi^1 , Mingqun Lin^1
and Yasuko Rikihisa^1
Summary
The inhibition of neutrophil apoptosis plays a central role in human
granulocytic anaplasmosis. Intracellular signalling pathways through
which the obligatory intracellular bacterium /Anaplasma phagocytophilum/
inhibits the spontaneous apoptosis of human peripheral blood neutrophils
were investigated. /bfl-1/ mRNA levels in uninfected neutrophils after
12 h in culture were reduced to = 5-25% of 0 h levels, but remained high
in infected neutrophils. The eukaryotic RNA synthesis inhibitor,
actinomycin D, prevented the maintenance of /bfl-1/ mRNA levels by /A.
phagocytophilum/. Differences in /mcl-1/, /bax/, /bcl-w/, /bad/ or /bak/
mRNA levels in infected versus uninfected neutrophils were not
remarkable. By using mitochondrial fluorescent dyes, Mitotracker Red and
JC-1, it was found that most uninfected neutrophils lost mitochondrial
membrane potential after 10-12 h incubation, whereas /A.
phagocytophilum/-infected neutrophils maintained high membrane
potential. Caspase 3 activity and the degree of apoptosis were lower in
dose-dependent manner in /A. phagocytophilum/-infected neutrophils at 16
h post infection, as compared to uninfected neutrophils. Anti-active
caspase 3 antibody labelling showed less positively stained population
in infected neutrophils compared to those in uninfected neutrophils
after 12 h incubation. These results suggest that /A. phagocytophilum/
inhibits human neutrophil apoptosis via transcriptional upregulation of
/bfl-1/ and inhibition of mitochondria-mediated activation of caspase 3
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