scholarly journals αvβ3 Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes

2000 ◽  
Vol 68 (10) ◽  
pp. 5673-5678 ◽  
Author(s):  
Jérôme Dellacasagrande ◽  
Eric Ghigo ◽  
Sarah Machergui-El ◽  
Hammami ◽  
Rudolf Toman ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Coxiella Burnetii ◽  
Tumor Necrosis ◽  
Q Fever ◽  
Polymyxin B ◽  
Bacterial Lipopolysaccharide ◽  
Host Cells ◽  
Αvβ3 Integrin ◽  
Human Monocytes ◽  
Necrosis Factor

ABSTRACT Coxiella burnetii, the agent of Q fever, enters human monocytes through αvβ3 integrin and survives inside host cells. In addition, C. burnetiistimulates the synthesis of inflammatory cytokines including tumor necrosis factor (TNF) by monocytes. We studied the role of the interaction of C. burnetii with THP-1 monocytes in TNF production. TNF transcripts and TNF release reached maximum values within 4 h. Almost all monocytes bound C. burnetiiafter 4 h, while the percentage of phagocytosing monocytes did not exceed 20%. Cytochalasin D, which prevented the uptake of C. burnetii without interfering with its binding, did not affect the expression of TNF mRNA. Thus, bacterial adherence, but not phagocytosis, is necessary for TNF production by monocytes. The monocyte αvβ3 integrin was involved in TNF synthesis since peptides containing RGD sequences and blocking antibodies against αvβ3 integrin inhibited TNF transcripts induced by C. burnetii. Nevertheless, the cross-linking of αvβ3 integrin by specific antibodies was not sufficient to induce TNF synthesis. The signal delivered by C. burnetii was triggered by bacterial lipopolysaccharide (LPS). Polymyxin B inhibited the TNF production stimulated by C. burnetii, and soluble LPS isolated fromC. burnetii largely mimicked viable bacteria. On the other hand, avirulent variants of C. burnetii induced TNF production through an increased binding to monocytes rather than through the potency of their LPS. We suggest that the adherence ofC. burnetii to monocytes via αvβ3 integrin enables surface LPS to stimulate TNF production in THP-1 monocytes.

scholarly journals Coxiella burnetii Survives in Monocytes from Patients with Q Fever Endocarditis: Involvement of Tumor Necrosis Factor

2000 ◽  
Vol 68 (1) ◽  
pp. 160-164 ◽  
Author(s):  
Jérôme Dellacasagrande ◽  
Eric Ghigo ◽  
Christian Capo ◽  
Didier Raoult ◽  
Jean-Louis Mege
Keyword(s):  
Tumor Necrosis Factor ◽  
Coxiella Burnetii ◽  
Tumor Necrosis ◽  
Q Fever ◽  
Healthy Controls ◽  
Bacterial Survival ◽  
Intracellular Killing ◽  
Bacterial Killing ◽  
Monocytes And Macrophages ◽  
Necrosis Factor

ABSTRACT Endocarditis is the most frequent form of chronic Q fever, an infectious disease caused by Coxiella burnetii. As this obligate intracellular bacterium inhabits monocytes and macrophages, we wondered if pathogenesis of Q fever endocarditis is related to defective intracellular killing of C. burnetii by monocytes. Monocytes from healthy controls eliminated virulent C. burnetii within 3 days. In contrast, monocytes from patients with ongoing Q fever endocarditis were unable to eliminate bacteria even after 6 days. In patients who were cured of endocarditis, the monocyte infection was close to that of control monocytes. This killing deficiency was not the consequence of generalized functional impairment, since patient monocytes eliminated avirulent C. burnetii as did control cells. The addition of supernatants ofC. burnetii-stimulated monocytes from patients with ongoing endocarditis to control monocytes enabled them to support C. burnetii survival, suggesting that some soluble factor is responsible for bacterial survival. This factor was related to tumor necrosis factor (TNF): expression of TNF mRNA and TNF release were increased in response to C. burnetii in patients with ongoing endocarditis compared to cured patients and healthy controls. In addition, neutralizing anti-TNF antibodies decreased C. burnetii internalization, an early step of bacterial killing, in monocytes from patients with ongoing endocarditis but did not affect delayed steps of intracellular killing. We suggest that Q fever-associated activation of monocytes allows the survival ofC. burnetii by modulating early phases of microbial killing.

Serotonin inhibition of tumor necrosis factor-α synthesis by human monocytes

Life Sciences ◽  
1991 ◽  
Vol 48 (26) ◽  
pp. 2557-2562 ◽  
Author(s):  
Eduardo Arzt ◽  
Mónica Costas ◽  
S. Finkielman ◽  
Victor E. Nahmod
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Human Monocytes ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Effects of botulinum toxin type D on secretion of tumor necrosis factor from human monocytes.

1989 ◽  
Vol 9 (5) ◽  
pp. 2239-2243 ◽  
Author(s):  
K Imamura ◽  
D Spriggs ◽  
T Ohno ◽  
D Kufe
Keyword(s):  
Botulinum Toxin ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Botulinum Toxin Type ◽  
Secretory Process ◽  
Detectable Effect ◽  
Human Monocytes ◽  
Type D ◽  
Necrosis Factor ◽  
Tnf Secretion

Botulinum toxins are potent neurotoxins which block the release of neurotransmitters. The effects of these toxins on hematopoietic cells, however, are unknown. Monocytes secrete a variety of polypeptide growth factors, including tumor necrosis factor (TNF). In the study reported here, the effects of botulinum toxin type D on the secretion of TNF from human monocytes were examined. The results demonstrate that botulinum toxin type D inhibits the release of TNF from monocytes activated by lipopolysaccharide (LPS) but not by 12-O-tetradecanoylphorbol-13-acetate. Botulinum toxin type D had no detectable effect on intracellular TNF levels in LPS-treated monocytes, indicating that the effects of this toxin involve the secretory process. This inhibitory effect of botulinum toxin type D on TNF secretion from LPS-treated monocytes was partially reversed by treatment with 12-O-tetradecanoylphorbol-13-acetate or introduction of guanosine 5'-[gamma-thio]triphosphate into these cells. The results demonstrate that TNF secretion is regulated by at least two distinct guanine nucleotide-binding proteins, one responsible for the activation of phospholipase C and another which acts as a substrate for botulinum toxin type D. ADP-ribosylation of monocyte membranes by botulinum toxin type D demonstrated the presence of three substrates with Mrs of 45,000, 21,000, and 17,000. While the role of these substrates in exocytosis is unknown, the results suggest that the Mr 21,000 substrate is involved in a process other than TNF secretion.

Polymyxin B Prevents Lipopolysaccharide-Induced Release of Tumor Necrosis Factor-  from Alveolar Macrophages

1989 ◽  
Vol 160 (1) ◽  
pp. 52-57 ◽  
Author(s):  
D. C. Stokes ◽  
J. L. Shenep ◽  
M. Fishman ◽  
W. K. Hildner ◽  
G. K. Bysani ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Alveolar Macrophages ◽  
Tumor Necrosis ◽  
Polymyxin B ◽  
Necrosis Factor

scholarly journals Human serum IgA downregulates the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) in human monocytes

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1278-1288 ◽  
Author(s):  
HM Wolf ◽  
MB Fischer ◽  
H Puhringer ◽  
A Samstag ◽  
E Vogel ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Serum Iga ◽  
Iga Antibodies ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract While the protective effect of IgA antibodies against infection of the mucosal surfaces is well documented, the mechanisms involved are not entirely clear. The aim of the current study is to investigate the effect of human serum IgA on the release of inflammatory cytokines in human monocytes activated with a particulate stimulus, Haemophilus influenzae type b (Hib), or soluble lipopolysaccharide (LPS) purified from Escherichia coli. Our results show that IgA downregulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, whereas IgG examined in parallel had no effect. IgA had no inhibitory effect on Hib-induced granulocyte-macrophage colony-stimulating factor release. TNF-alpha and IL-6 release were downmodulated if IgA was present during cytokine induction, and IgA was also inhibitory if added to Hib-pretreated monocytes during the phase of cytokine release. These findings indicate that there are at least two mechanisms whereby IgA antibodies can downregulate TNF-alpha and IL-6 release in human monocytes: by a mechanism acting during the time of monocyte activation, and a mechanism that downregulates the production and/or the release of these cytokines in activated monocytes. Regulation of TNF-alpha and IL-6 release by IgA may be among the antiinflammatory mechanisms preventing an uncontrolled release of potentially noxious levels of inflammatory cytokines during acute and/or chronic inflammation.

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