Tumor necrosis factor-α and nitrite/nitrate responses during acute mastitis induced by Escherichia coli infection and endotoxin in dairy cows

Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates.

Download Full-text

Verotoxin 1 from Escherichia coli Affects Gb3/CD77+ Bovine Lymphocytes Independent of Interleukin-2, Tumor Necrosis Factor-α, and Interferon-α

Experimental Biology and Medicine ◽

10.1177/153537020322800408 ◽

2003 ◽

Vol 228 (4) ◽

pp. 377-386 ◽

Cited By ~ 19

Author(s):

Christian Menge ◽

Ivonne Stamm ◽

Maike Blessenohl ◽

Lothar H. Wieler ◽

Georg Baljer

Keyword(s):

Escherichia Coli ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Interleukin 2 ◽

Γδ T Cells ◽

Interferon Α ◽

Bovine Lymphocytes ◽

Factor Α ◽

Necrosis Factor

Verotoxin (VT)-induced immunomodulation has been implicated in the ability of VT-producing Escherichia coli (VTEC) to cause persistent infections in cattle. VT1, also referred to as Shiga toxin 1, is a potent cytotoxin that modulates cytokine secretions and functions. This prompted the current investigation to examine whether the inhibiting effect of VT1 on bovine lymphocytes correlates with the expression of the cellular VT1 receptor Gb3/CD77 or is mediated instead via perturbation of cytokine secretion. Using blood mononuclear cells stimulated by mitogens as a model, VT1 significantly blocked lymphoblast transformation and proliferation in the BoCD8+ T cell and BoCD21+ B cell population. In contrast, VT1 dramatically reduced the number of viable Gb3/CDTZ+ blast cells within all subpopulations identified (BoCD2+, BoCD4+, BoCD8+, WC1+ [i.e., γδ T cells] BoCD21+, and BoCD25+). Similar effects of VT1 were observed when the culture medium was supplemented with selected cytokines: tumor necrosis factor-α-sensitizing endothelial cells against VT1, interferon-a (IFN-α) as bovine IFN-α receptors are partially homologous to the B-subunit of VT1, and interleukin-2 that is critical for lymphocyte proliferation in vitro. The addition of these cytokines was neither able to mimic nor to overcome the effects of VT1. Therefore, it is concluded that VT1 directly acts on bovine lymphocytes rather than inducing a cytokine-mediated effect. VT1 considerably affects all main bovine lymphocyte subpopulations, implicating that the immune system is a predominant target for VT1 In cattle.

Download Full-text

Increased elastase release by CF neutrophils is mediated by tumor necrosis factor-α and interleukin-8

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2000.278.1.l33 ◽

2000 ◽

Vol 278 (1) ◽

pp. L33-L41 ◽

Cited By ~ 72

Author(s):

Clifford Taggart ◽

Raymond J. Coakley ◽

Peter Greally ◽

Gerry Canny ◽

Shane J. O'Neill ◽

...

Keyword(s):

Escherichia Coli ◽

Cystic Fibrosis ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Normal Subjects ◽

Tnf Α ◽

Blood Neutrophils ◽

Factor Α ◽

Necrosis Factor

Cystic fibrosis (CF) is a lethal, hereditary disorder characterized by a neutrophil-dominated inflammation of the lung. We sought to determine whether neutrophils from individuals with CF release more neutrophil elastase (NE) than neutrophils from normal subjects. Our results showed that peripheral blood neutrophils (PBNs) from normal subjects and individuals with CF contained similar amounts of NE, but after preincubation with CF bronchoalveolar lavage (BAL) fluid, significantly more NE was released by CF PBNs, a release that was amplified further by incubation with opsonized Escherichia coli. To determine which components of CF BAL fluid stimulated this excessive NE release from CF PBNs, we repeated the experiments after neutralization or immunoprecipitation of tumor necrosis factor (TNF)-α and interleukin (IL)-8 in CF BAL fluid. We found that subsequent NE release from CF PBNs was reduced significantly when TNF-α and IL-8 were removed from CF BAL fluid. When TNF-α and IL-8 were used as activating stimuli, CF PBNs released significantly greater amounts of NE compared with PBNs from control subjects and individuals with bronchiectasis. These results indicate that CF PBNs respond abnormally to TNF-α and IL-8 in CF BAL fluid and react to opsonized bacteria by releasing more NE. This may help explain the increased NE burden seen in this condition.

Download Full-text

Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.5.r1356 ◽

2001 ◽

Vol 280 (5) ◽

pp. R1356-R1363 ◽

Cited By ~ 10

Author(s):

L. Fang ◽

B. Nowicki ◽

C. Yallampalli

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Intrauterine Infection ◽

Uterine Horn ◽

No Production ◽

Pregnant Rats ◽

Escherichia Coli Infection ◽

Factor Α ◽

Necrosis Factor

Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-α protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-α protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-α after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and that the constitutively elevated uterine NO during pregnancy may help contain or even reduce the risk of infection-related complications.

Download Full-text