Serum amyloid A is an innate immune opsonin for Gram-negative bacteria

Shah, Chandrabala; Hari-Dass, Ranjeeta; Raynes, John G.

doi:10.1182/blood-2005-11-011932

Cited by 214 publications

(171 citation statements)

References 36 publications

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“…SAA1 and pro-inflammatory chemokines IL8, CCL2, CXCL5, CXCL3, CXCL2 and CCL8 belong to the top-ten most up-regulated genes (see Table 3), SAA1 being the most up-regulated gene with a 27-fold change by comparison to mock-stimulated PBMCs. SAA1 encodes the major acute-phase protein Serum Amyloid A (SAA), the precise role of which is still unclear despite reports suggesting a key role in the establishment and maintenance of inflammation notably as an antiapoptotic agent for neutrophils [36] and as an opsonin that would facilitate phagocytosis of gram-negative bacteria [37]. SAA1 was also found as the most up-regulated gene in spleen seven days after infection by H. parasuis [9].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response

et al. 2010

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BackgroundDesigning sustainable animal production systems that better balance productivity and resistance to disease is a major concern. In order to address questions related to immunity and resistance to disease in pig, it is necessary to increase knowledge on its immune system and to produce efficient tools dedicated to this species.ResultsA long-oligonucleotide-based chip referred to as SLA-RI/NRSP8-13K was produced by combining a generic set with a newly designed SLA-RI set that targets all annotated loci of the pig major histocompatibility complex (MHC) region (SLA complex) in both orientations as well as immunity genes outside the SLA complex.The chip was used to study the immune response of pigs following stimulation of porcine peripheral blood mononuclear cells (PBMCs) with lipopolysaccharide (LPS) or a mixture of phorbol myristate acetate (PMA) and ionomycin for 24 hours. Transcriptome analysis revealed that ten times more genes were differentially expressed after PMA/ionomycin stimulation than after LPS stimulation. LPS stimulation induced a general inflammation response with over-expression of SAA1, pro-inflammatory chemokines IL8, CCL2, CXCL5, CXCL3, CXCL2 and CCL8 as well as genes related to oxidative processes (SOD2) and calcium pathways (S100A9 and S100A12). PMA/ionomycin stimulation induced a stronger up-regulation of T cell activation than of B cell activation with dominance toward a Th1 response, including IL2, CD69 and TNFRSF9 (tumor necrosis factor receptor superfamily, member 9) genes. In addition, a very intense repression of THBS1 (thrombospondin 1) was observed. Repression of MHC class I genes was observed after PMA/ionomycin stimulation despite an up-regulation of the gene cascade involved in peptide processing. Repression of MHC class II genes was observed after both stimulations. Our results provide preliminary data suggesting that antisense transcripts mapping to the SLA complex may have a role during immune response.ConclusionThe SLA-RI/NRSP8-13K chip was found to accurately decipher two distinct immune response activations of PBMCs indicating that it constitutes a valuable tool to further study immunity and resistance to disease in pig. The transcriptome analysis revealed specific and common features of the immune responses depending on the stimulation agent that increase knowledge on pig immunity.

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Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response

et al. 2010

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“…Indeed, SAA has been shown to bind to the outer membrane protein A of a large number of Gram-negative bacteria and to be involved in opsonization of these bacteria. 32,33 The observations that SAA binds to HCV and has an antiviral activity against this virus provide experimental evidence that SAA can have a direct effect against pathogens. This observation is in favor of a role for SAA in the innate immune response against HCV.…”

Section: Discussionmentioning

confidence: 99%

Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system

et al. 2006

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Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/ jpages/0270-9139/suppmat/index.html).

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“…The antibacterial SAA protein is an opsonin for gram-negative bacteria (Shah et al, 2006), and because of its massive increase during mastitis it has been suggested as a biomarker for this disease (Larsen et al, 2010).…”

Section: Pathogen Differencesmentioning

confidence: 99%

Microfluidic high-throughput RT-qPCR measurements of the immune response of primary bovine mammary epithelial cells cultured from milk to mastitis pathogens

Sorg

Danowski

Korenkova

et al. 2013

Animal

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Bovine mastitis, the inflammation of the udder, is a major problem for the dairy industry and for the welfare of the animals. To better understand this disease, and to implement two special techniques for studying mammary gland immunity in vitro, we measured the innate immune response of primary bovine mammary epithelial cells (pbMEC) from six Brown Swiss cows after stimulation with the heat-inactivated mastitis pathogens, Escherichia coli 1303 and Staphylococcus aureus 1027. The cells were extracted and cultivated from milk instead of udder tissue, which is usually done. The advantages of this technique are non-invasiveness and less contamination by fibroblasts. For the first time, pbMEC gene expression (GE) was measured with a microfluidic high-throughput real-time reverse transcription-quantitative PCR platform, the BioMark HD TM system from Fluidigm. In addition to the physiological analysis, the precision and suitability of this method was evaluated in a large data set. The mean coefficient of variance (6 s.e.) between repeated chips was 4.3 6 0.4% for highly expressed and 3.3 6 0.4% for lowly expressed genes. Quantitative PCR (qPCR) replicate deviations were smaller than the cell culture replicate deviations, indicating that biological and cell culture differences could be distinguished from the background noise. Twenty-two genes (complement system, chemokines, inflammatory cytokines, antimicrobial peptides, acute phase response and toll-like receptor signalling) were differentially expressed (P , 0.05) with E. coli. The most upregulated gene was the acute phase protein serum amyloid A3 with 618-time fold. S. aureus slightly induced CCL5, IL10, TLR4 and S100A12 expression and failed to elicit a distinct overall innate immune response. We showed that, with this milk-derived pbMEC culture and the high-throughput qPCR technique, it is possible to obtain similar results in pbMEC expression as with conventional PCR and with satisfactory precision so that it can be applied in future GE studies in pbMEC.Keywords: bovine mastitis, gene expression profiling, microfluidic qPCR, primary bovine mammary epithelial cells, innate immune response ImplicationsWe show that a time-and cost-efficient high-throughput quantitative PCR (qPCR) system, applied on primary bovine mammary epithelial cells (pbMEC) cultured from milk, is a convenient alternative to the two major standard procedures in measuring gene expression. We obtained similar results as studies with pbMEC from udder tissue and measurements on DNA microarrays or conventional qPCR. We suggest that the milk-derived pbMEC culture and the microfluidic high-throughput qPCR system could be applied in future experiments with pbMEC.

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Serum amyloid A is an innate immune opsonin for Gram-negative bacteria

Cited by 214 publications

References 36 publications

Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response

Transcriptome analysis of porcine PBMCs after in vitro stimulation by LPS or PMA/ionomycin using an expression array targeting the pig immune response

Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system

Microfluidic high-throughput RT-qPCR measurements of the immune response of primary bovine mammary epithelial cells cultured from milk to mastitis pathogens

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