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

The recruitment of circulating endothelial progenitor cells (EPCs)might have a beneficial effect on the clinical course of severaldiseases. Endothelial damage and detachment of endothelial cells areknown to occur in infection, tissue ischemia, and sepsis. These detrimentaleffects in EPCs are unknown. Here we elucidated whetherhuman EPCs internalize Bartonella henselae constituting a circulatingniche of the pathogen. B. henselae invades EPCs as shown by gentamicinprotection assays and transmission electron microscopy(TEM). Dil-Ac-LDL/lectin double immunostaining and fluorescenceactivatedcell sorting (FACS) analysis of EPCs revealed EPC bioactivityafter infection with B. henselae. Nitric oxide (NO) and its precursorL-arginine (L-arg) exert a plethora of beneficial effects on vascularfunction and modulation of immune response. Therefore, we testedalso the hypothesis that L-arg (1–30 mM) would affect the infection ofB. henselae or tumor necrosis factor (TNF) in EPCs. Our data provideevidence that L-arg counteracts detrimental effects induced by TNF orBartonella infections via NO (confirmed by DETA-NO and L-NMMAexperiments) and by modulation of p38 kinase phosphorylation.Microarray analysis indicated several genes involved in immuneresponse were differentially expressed in Bartonella-infected EPCs,whereas these genes returned in steady state when cells wereexposed to sustained doses of L-arg. This mechanism may have broadtherapeutic applications in tissue ischemia, angiogenesis, immuneresponse, and sepsis.