Abstract
The recruitment of circulating endothelial progenitor cells (EPCs) might have a beneficial effect on the clinical course of several diseases. Endothelial damage and detachment of endothelial cells are known to occur in infection, tissue ischemia, and sepsis. These detrimental effects in EPCs are unknown. Here we elucidated whether human EPCs internalize Bartonella henselae constituting a circulating niche of the pathogen. B. henselae invades EPCs as shown by gentamicin protection assays and transmission electron microscopy (TEM). Dil-Ac-LDL/lectin double immunostaining and fluorescence-activated cell sorting (FACS) analysis of EPCs revealed EPC bioactivity after infection with B. henselae. Nitric oxide (NO) and its precursor L-arginine (L-arg) exert a plethora of beneficial effects on vascular function and modulation of immune response. Therefore, we tested also the hypothesis that L-arg (1-30 mM) would affect the infection of B. henselae or tumor necrosis factor (TNF) in EPCs. Our data provide evidence that L-arg counteracts detrimental effects induced by TNF or Bartonella infections via NO (confirmed by DETA-NO and L-NMMA experiments) and by modulation of p38 kinase phosphorylation. Microarray analysis indicated several genes involved in immune response were differentially expressed in Bartonella-infected EPCs, whereas these genes returned in steady state when cells were exposed to sustained doses of L-arg. This mechanism may have broad therapeutic applications in tissue ischemia, angiogenesis, immune response, and sepsis.
| Original language | English |
|---|---|
| Pages (from-to) | 9427-9432 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 105 |
| Issue number | 27 |
| DOIs | |
| Publication status | Published - Jul 8 2008 |
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Keywords
- Immune response
- Sepsis
ASJC Scopus subject areas
- Genetics
- General
Cite this
Detrimental effects of Bartonella henselae are counteracted by L-arginine and nitric oxide in human endothelial progenitor cells. / Salvatore, Paola; Casamassimi, Amelia; Sommese, Linda; Fiorito, Carmela; Ciccodicol, Alfredo; Rossiello, Raffaele; Avallone, Bice; Grimaldi, Vincenzo; Costa, Valerio; Rienzo, Monica; Colicchio, Roberta; Williams-Ignarro, Sharon; Pagliarulo, Caterina; Prudente, Maria Evelina; Abbondanza, Ciro; Lamberti, Florentia; Baroni, Adone; Buommino, Elisabetta; Farzati, Bartolomeo; Tufano, Maria Antonietta; Ignarro, Louis Joseph; Napoli, Claudio.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 27, 08.07.2008, p. 9427-9432.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Detrimental effects of Bartonella henselae are counteracted by L-arginine and nitric oxide in human endothelial progenitor cells
AU - Salvatore, Paola
AU - Casamassimi, Amelia
AU - Sommese, Linda
AU - Fiorito, Carmela
AU - Ciccodicol, Alfredo
AU - Rossiello, Raffaele
AU - Avallone, Bice
AU - Grimaldi, Vincenzo
AU - Costa, Valerio
AU - Rienzo, Monica
AU - Colicchio, Roberta
AU - Williams-Ignarro, Sharon
AU - Pagliarulo, Caterina
AU - Prudente, Maria Evelina
AU - Abbondanza, Ciro
AU - Lamberti, Florentia
AU - Baroni, Adone
AU - Buommino, Elisabetta
AU - Farzati, Bartolomeo
AU - Tufano, Maria Antonietta
AU - Ignarro, Louis Joseph
AU - Napoli, Claudio
PY - 2008/7/8
Y1 - 2008/7/8
N2 - The recruitment of circulating endothelial progenitor cells (EPCs) might have a beneficial effect on the clinical course of several diseases. Endothelial damage and detachment of endothelial cells are known to occur in infection, tissue ischemia, and sepsis. These detrimental effects in EPCs are unknown. Here we elucidated whether human EPCs internalize Bartonella henselae constituting a circulating niche of the pathogen. B. henselae invades EPCs as shown by gentamicin protection assays and transmission electron microscopy (TEM). Dil-Ac-LDL/lectin double immunostaining and fluorescence-activated cell sorting (FACS) analysis of EPCs revealed EPC bioactivity after infection with B. henselae. Nitric oxide (NO) and its precursor L-arginine (L-arg) exert a plethora of beneficial effects on vascular function and modulation of immune response. Therefore, we tested also the hypothesis that L-arg (1-30 mM) would affect the infection of B. henselae or tumor necrosis factor (TNF) in EPCs. Our data provide evidence that L-arg counteracts detrimental effects induced by TNF or Bartonella infections via NO (confirmed by DETA-NO and L-NMMA experiments) and by modulation of p38 kinase phosphorylation. Microarray analysis indicated several genes involved in immune response were differentially expressed in Bartonella-infected EPCs, whereas these genes returned in steady state when cells were exposed to sustained doses of L-arg. This mechanism may have broad therapeutic applications in tissue ischemia, angiogenesis, immune response, and sepsis.
AB - The recruitment of circulating endothelial progenitor cells (EPCs) might have a beneficial effect on the clinical course of several diseases. Endothelial damage and detachment of endothelial cells are known to occur in infection, tissue ischemia, and sepsis. These detrimental effects in EPCs are unknown. Here we elucidated whether human EPCs internalize Bartonella henselae constituting a circulating niche of the pathogen. B. henselae invades EPCs as shown by gentamicin protection assays and transmission electron microscopy (TEM). Dil-Ac-LDL/lectin double immunostaining and fluorescence-activated cell sorting (FACS) analysis of EPCs revealed EPC bioactivity after infection with B. henselae. Nitric oxide (NO) and its precursor L-arginine (L-arg) exert a plethora of beneficial effects on vascular function and modulation of immune response. Therefore, we tested also the hypothesis that L-arg (1-30 mM) would affect the infection of B. henselae or tumor necrosis factor (TNF) in EPCs. Our data provide evidence that L-arg counteracts detrimental effects induced by TNF or Bartonella infections via NO (confirmed by DETA-NO and L-NMMA experiments) and by modulation of p38 kinase phosphorylation. Microarray analysis indicated several genes involved in immune response were differentially expressed in Bartonella-infected EPCs, whereas these genes returned in steady state when cells were exposed to sustained doses of L-arg. This mechanism may have broad therapeutic applications in tissue ischemia, angiogenesis, immune response, and sepsis.
KW - Immune response
KW - Sepsis
UR - http://www.scopus.com/inward/record.url?scp=48249103955&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48249103955&partnerID=8YFLogxK
U2 - 10.1073/pnas.0803602105
DO - 10.1073/pnas.0803602105
M3 - Article
C2 - 18595894
AN - SCOPUS:48249103955
VL - 105
SP - 9427
EP - 9432
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 27
ER -