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

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

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Keywords

  • Immune response
  • Sepsis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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, M. E., Abbondanza, C., Lamberti, F., Baroni, A., Buommino, E., Farzati, B., ... 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, 105(27), 9427-9432. https://doi.org/10.1073/pnas.0803602105