Cellular changes and induction of apoptosis in human promyelocytic HL-60 cells infected with the agent of human granulocytic ehrlichiosis (HGE).
Human granulocytic ehrlichiosis (HGE) is an emerging and occasionally fatal human infectious disease whose pathogenesis is largely unknown. Goodman et al. (1) recently described the successful cultivation of the HGE infectious agent in human promyelocytic HL-60 leukemic cells. It was reported in the same study that infectivity invariably led to host cell death, although the mechanism by which HGE infection triggers cellular self-destruction is as yet undetermined. In this communication, we show that in vitro passage of HGE pathogen-infected blood elicits a significantly dysfunctional G1-to-S transition. Moreover, we provide evidence that the cytopathic properties of the HGE pathogen are attributed to its ability to induce apoptosis in host HL-60 cells. Determination of specific protein expression changes by Western blot analysis showed that HGE infection resulted in reduced expression of PCNA and pRB, both of which play a role in cell cycling. Moreover, the steady state level of bcl-2, which protects eukaryotic cells against apoptosis, is suppressed by exposure to the HGE agent. These results suggest that this pathogen HGE induces apoptosis in HL-60 cells by a mechanism involving the shut-off of multiple cell cycle and apoptosis regulatory events.
Hsieh
T C
TC
Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla 10595, USA.
Aguero-Rosenfeld
M E
ME
Wu
J M
JM
Ng
C
C
Papanikolaou
N A
NA
Varde
S A
SA
Schwartz
I
I
Pizzolo
J G
JG
Melamed
M
M
Horowitz
H W
HW
Nadelman
R B
RB
Wormser
G P
GP
D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D004536:Ehrlichia / Q000254:growth & development / Q000302:isolation & purification*; D016873:Ehrlichiosis / Q000097:blood / Q000382:microbiology / Q000473:pathology; D006098:Granulocytes / Q000382:microbiology / Q000473:pathology; D018922:HL-60 Cells / Q000382:microbiology* / Q000473:pathology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000382:microbiology / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis
D018809:Proliferating Cell Nuclear Antigen