Detrimental effects of Bartonella henselae are counteracted by L-arginine and nitric oxide in human endothelial progenitor cells

Paola Salvatore, Amelia Casamassimi, Linda Sommese, Carmela Fiorito, Alfredo Ciccodicol, Raffaele Rossiello, Bice Avallone, Vincenzo Grimaldi, Valerio Costa, Monica Rienzo, Roberta Colicchio, Sharon Williams-Ignarro, Caterina Pagliarulo, Maria Evelina Prudente, Ciro Abbondanza, Florentia Lamberti, Adone Baroni, Elisabetta Buommino, Bartolomeo Farzati, Maria Antonietta TufanoLouis Joseph Ignarro, Claudio Napoli

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 languageEnglish
Pages (from-to)9427-9432
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number27
DOIs
Publication statusPublished - Jul 8 2008

Fingerprint

Bartonella henselae
Arginine
Nitric Oxide
Sepsis
Ischemia
Tumor Necrosis Factor-alpha
Infection
Bartonella Infections
DEET
Bartonella
omega-N-Methylarginine
Endothelial Progenitor Cells
Microarray Analysis
Gentamicins
Transmission Electron Microscopy
Lectins
Genes
Blood Vessels
Flow Cytometry
Phosphotransferases

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 journalArticle

Salvatore, P, Casamassimi, A, Sommese, L, Fiorito, C, Ciccodicol, A, Rossiello, R, Avallone, B, Grimaldi, V, Costa, V, Rienzo, M, Colicchio, R, Williams-Ignarro, S, Pagliarulo, C, Prudente, ME, Abbondanza, C, Lamberti, F, Baroni, A, Buommino, E, Farzati, B, Tufano, MA, Ignarro, LJ & Napoli, C 2008, 'Detrimental effects of Bartonella henselae are counteracted by L-arginine and nitric oxide in human endothelial progenitor cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 27, pp. 9427-9432. https://doi.org/10.1073/pnas.0803602105
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. / Detrimental effects of Bartonella henselae are counteracted by L-arginine and nitric oxide in human endothelial progenitor cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 27. pp. 9427-9432.
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AU - Ciccodicol, Alfredo

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AU - Grimaldi, Vincenzo

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AU - Rienzo, Monica

AU - Colicchio, Roberta

AU - Williams-Ignarro, Sharon

AU - Pagliarulo, Caterina

AU - Prudente, Maria Evelina

AU - Abbondanza, Ciro

AU - Lamberti, Florentia

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AU - Buommino, Elisabetta

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