Article

Effect of recombinant Panton-Valentine leukocidin in vitro on apoptosis and cytokine production of human alveolar macrophages.

Department of Internal Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P R China.
Canadian Journal of Microbiology (impact factor: 1.36). 03/2010; 56(3):229-35. DOI:10.1139/w10-002 pp.229-35
Source: PubMed

ABSTRACT Panton-Valentine leukocidin (PVL) is associated with rare cases of necrotizing pneumonia that occur in otherwise healthy individuals. Human alveolar macrophages (HAMs) are major effector cells in host defense against infections. However, the impact of PVL on HAMs is uncertain. We evaluated the role of PVL in cytotoxicity and production of inflammatory cytokines secreted by HAMs. HAMs were purified from bronchoalveolar lavage fluid. Recombinant PVL (rPVL) was used in the study to interfere with HAM apoptosis and cytokine production in vitro. Hoechst 33342 fluorescence staining, transmission electron microscopy examination, and flow cytometry indicated that rPVL (10 nmol/L) treatment resulted in HAMs with markedly apoptotic characteristics, and HAMs treated with rPVL at 100 nmol/L showed clear indication of necrosis. A treatment of rPVL at 10 nmol/L elicited the secretion of IL-10 by HAMs relative to untreated control cells, but there was a slight decrease in the constitutive secretion of tumor necrosis factor (TNF)-alpha. Our results indicate that PVL-treated samples decreased HAM viability, leading to apoptosis at low concentrations and necrosis at high concentrations. In addition, PVL-treated cells released increased amounts of IL-10 and decreased amounts of TNF-alpha under apoptosis-inducing concentrations. Therefore, we speculated that PVL could play a negative role in HAM function at lower concentrations.

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    Article: Staphylococcal Panton-Valentine leukocidin induces pro-inflammatory cytokine production and nuclear factor-kappa B activation in neutrophils.
    Xiaoling Ma, Wenjiao Chang, Cuiping Zhang, Xin Zhou, Fangyou Yu
    [show abstract] [hide abstract]
    ABSTRACT: Panton-Valentine leukocidin (PVL) is a cytotoxin secreted by Staphylococcus aureus and associated with severe necrotizing infections. PVL targets polymorphonuclear leukocytes, especially neutrophils, which are the first line of defense against infections. Although PVL can induce neutrophil death by necrosis or apoptosis, the specific inflammatory responses of neutrophils to this toxin are unclear. In this study, both in vivo and in vitro studies demonstrated that recombinant PVL has an important cytotoxic role in human neutrophils, leading to apoptosis at low concentrations and necrosis at high concentrations. Recombinant PVL also increased the levels of pro-inflammatory cytokine secretion from neutrophils. The up-regulation of pro-inflammatory cytokines was due to nuclear factor-kappa B (NF-κB) activation induced by PVL. Moreover, blocking NF-κB inhibited the production of inflammatory cytokines. To test the role of neutrophil immune responses during the pathogenesis of PVL-induced acute lung injury, we used immunocompetent or neutropenic rabbits to develop a model of necrotizing pneumonia. Immunocompetent rabbits challenged with PVL demonstrated increased inflammation containing neutrophilic infiltrates. In addition, there were elevated levels of inflammatory cytokines (IL-6, IL-8, TNF-α and IL-10) and NF-κB in the lung homogenate. In contrast, the lung tissues from neutropenic rabbits contained mild or moderate inflammation, and the levels of inflammatory cytokines and NF-κB increased only slightly. Data from the current study support growing evidence that neutrophils play an important role in the pathogenesis of PVL-induced tissue injury and inflammation. PVL can stimulate neutrophils to release pro-inflammatory mediators, thereby causing an acute inflammatory response. The ability of PVL to induce inflammatory cytokine release may be associated with the activation of NF-κB or its pore-forming properties.
    PLoS ONE 01/2012; 7(4):e34970. · 4.09 Impact Factor
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Keywords

10 nmol/L elicited
 
bronchoalveolar lavage fluid
 
clear indication
 
cytokine production
 
flow cytometry
 
HAM apoptosis
 
HAM viability
 
HAMs
 
Hoechst 33342 fluorescence staining
 
host defense
 
Human alveolar macrophages
 
inflammatory cytokines secreted
 
lower concentrations
 
markedly apoptotic characteristics
 
negative role
 
PVL-treated samples
 
rare cases
 
transmission electron microscopy examination
 
tumor necrosis factor
 
untreated control cells
 

Benquan Wu