Bartonella quintana lipopolysaccharide effects on leukocytes, CXC chemokines and apoptosis: a study on the human whole blood and a rat model.
Bartonella quintana, an emerging gram-negative pathogen, may cause trench fever, endocarditis, cerebral abscess and bacillary angiomatosis usually with the absence of septic shock in humans. B. quintana lipopolysaccharide (LPS), a deep rough endotoxin with strong reactivity in the limulus amebocyte lysate (LAL)-assay, was studied in human whole blood and in a rat model. A significant (P<0.05) increase of interleukin-8 (IL-8) concentration, comparable to the level induced by enterobacterial LPS, was stimulated in the human whole blood by B. quintana LPS. Isolated human neutrophils delayed their apoptotic behavior in the presence of B. quintana LPS. In the rat, B. quintana LPS induced a significant (P<0.001) increase in white blood cell count, both 30 and 60 min after intravenous injection. Such leukocytosis was inhibited by pretreatment with prazosin, an alpha-adrenergic antagonist. B. quintana LPS did not significantly change heart rate (HR), hematocrit (HCT) and platelet count in the above reported in vivo model, and regarding mean blood pressure (MAP) only a very early (5 min after LPS) and mild (yet significant) hypotension was observed. In contrast, a long-lasting decrease of MAP was found in Salmonella minnesota R595 LPS-treated animals. Blood TNFalpha levels did not change significantly from the baseline in rats injected with either saline or with B. quintana LPS, on the contrary S. minnesota R595 LPS-injected animals showed substantial increase of TNFalpha levels up to 2924 pg/ml at 60 min after LPS injection. B. quintana LPS as well as Salmonella LPS-injected rats exhibited an increase of the blood levels of GRO/CINC-1, particularly at 240 min after LPS administration. Apical part of rat gut villi showed several TUNEL-positive cells in tissue sections from B. quintana LPS-treated animals. Taken together, our data demonstrates that B. quintana LPS is able to selectively stimulate some inflammatory mediators. B. quintana LPS-induced leukocytosis appears mediated by an alpha-adrenergic receptor. The delayed apoptotic process of leukocytes and the chemokine increase may explain the apoptotic cells found in the rat gut and the inflammatory reactions in some human Bartonella diseases. This peculiar inflammatory pattern induced by B. quintana LPS, may partially account for the lack of severe septic shock, observed in human B. quintana infections.
Matera
Giovanni
G
Institute of Microbiology, Department of Medical Sciences, Faculty of Medicine, University of Catanzaro, Via T. Campanella 115, I-88100, Catanzaro, Italy.
Liberto
Maria Carla
MC
Quirino
Angela
A
Barreca
Giorgio Settimo
GS
Lamberti
Angelo Giuseppe
AG
Iannone
Michelangelo
M
Mancuso
Eliana
E
Palma
Ernesto
E
Cufari
Francesco Antonio
FA
Rotiroti
Domenicantonio
D
Focà
Alfredo
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001473:Bartonella / Q000737:chemistry*; D001772:Blood Cell Count; D019743:Chemokines, CXC / Q000378:metabolism*; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects*; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010976:Platelet Count; D011224:Prazosin / Q000494:pharmacology; D011513:Proteus mirabilis / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012475:Salmonella / Q000737:chemistry
D019743:Chemokines, CXC; D004731:Endotoxins; D018836:Inflammation Mediators; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011224:Prazosin