scholarly journals PSII-29 Identification of serum proteins that interact with extracellular histones in feedlot cattle

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 246-246
Author(s):  
Victor V Flores ◽  
Jennifer A Hernandez Gifford ◽  
Julia Matera ◽  
Steven Hartson ◽  
Blake K Wilson ◽  
...  

Abstract Bovine respiratory disease complex remains the largest challenge facing the cattle industry. Extracellular histones, which are released during disease, have a pathological role in death associated with acute sepsis or respiratory distress syndrome. Treatment against histone cytotoxicity improves survivability of mice suffering from sepsis and respiratory disease. Previously, we demonstrated calves with severe or lethal cases of bovine respiratory disease had an impaired capacity to protect against histone cytotoxicity. However, the mechanism or component of the serum which modulates histone cytotoxicity is unclear. Therefore, the objective of the current study was to identify components in serum which interact with extracellular histones. To achieve this objective serum proteins that interact with histones were precipitated by the addition and incubation of exogenous histones (2.5μg/μL; 1 h; 23°C). Serum protective capacity was determined pre- and post-precipitation, using our novel in-vitro assay and cell viability was estimated using resazurin. Fluorescent values were analyzed using GLM procedure of SAS and means were separated using PDIFF function. Fluorescent values decreased (P < 0.05) after precipitation, indicating interacting proteins were effectively precipitated. Protein from the precipitate was then separated using SDS-PAGE. Proteomes, excluding IgG and BSA, were analyzed by LC-MS/MS using a label-free data-dependent “shotgun” mass spectrometry approach. Proteins were identified and quantified by searching UniProtKB database (restricted to Bos taurus; 32,967 entries) using Andromeda search engine in MaxQuant. Seven of the top twenty candidate proteins identified were associated with the complement system. Results in the literature suggest that histones play a role in controlling activation of the complement system through binding of complement associated proteins. Results from the current study extend those findings and suggest the complement system may interact with extracellular histones to minimize histone cytotoxicity, indicating aberrant regulation of the complement system or extracellular histones can lead to increased tissue damage during disease.

2015 ◽  
Vol 93 (4) ◽  
pp. 1841-1849
Author(s):  
J. A. Matera ◽  
B. K. Wilson ◽  
J. A. Hernandez Gifford ◽  
D. L. Step ◽  
C. R. Krehbiel ◽  
...  

Abstract Bovine respiratory disease complex (BRDC) is the leading cause of morbidity and mortality in feedlot cattle. Significant inflammation and lesions are often observed in lungs of infected cattle. During acute inflammatory responses, histones contribute to mortality in rodents and humans and serum proteins can protect against histone-induced cytotoxicity. We hypothesized that cattle experiencing chronic or fatal cases of BRDC have reduced ability to protect against cytotoxic effects of histones. Serum samples were collected from 66 bull calves at the time of normal feedlot processing procedures. Animals were retrospectively assigned to groups consisting of calves never treated for BRDC (control [CONT]; n = 10), calves treated with antimicrobials once for BRDC (1T; n = 16), calves treated twice for BRDC (2T; n = 13), calves treated 3 times for BRDC (3T; n = 14), or calves treated 4 times for BRDC (4T; n = 13). Samples were also collected each time animals received antimicrobial treatment; animals within a group were further sorted by calves that recovered and calves that died to test histone cytotoxicity. Bovine kidney cells were cultured in duplicate in 96-well plates and exposed to 0 or 50 μg/mL of total histones for 18 h with 1% serum from each animal. Cell viability was assessed by the addition of resazurin for 6 h followed by fluorescent quantification. Fluorescent values from serum alone were subtracted from values obtained for histone treatment for each animal. Serum from CONT, 1T, and 2T at initial processing all exhibited a similar (P > 0.10) response to histone treatment with fluorescent values of –312 ± 557, –1,059 ± 441, and –975 ± 489, respectively. However, 3T and 4T demonstrated an impaired capacity (P < 0.05) to protect against histones (–2,778 ± 471 and –3,026 ± 489) at initial processing when compared to the other groups. When sorted by mortality within group, calves that were treated twice and recovered (–847 ± 331) demonstrated a greater (P < 0.05) protective capacity than calves that were treated twice and died (–2,264 ± 412), indicating that calves that contract BRDC and ultimately die might have reduced protective capacity against histone cytotoxicity. Results suggest that calves that require multiple treatments for BRDC have reduced ability to protect against cytotoxicity of histones. Understanding the primary mechanism responsible for protecting against histone cytotoxicity could lead to improved identification of animals susceptible to severe cases of BRDC, improved focus and use of available resources, or better treatments for severe cases of BRDC.


2019 ◽  
Vol 20 (2) ◽  
pp. 163-181
Author(s):  
A. M. O'Connor ◽  
D. Hu ◽  
S. C. Totton ◽  
N. Scott ◽  
C. B. Winder ◽  
...  

AbstractWe conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.


Vaccine ◽  
2016 ◽  
Vol 34 (30) ◽  
pp. 3478-3492 ◽  
Author(s):  
R.W. Fulton ◽  
J.M. d’Offay ◽  
C. Landis ◽  
D.G. Miles ◽  
R.A. Smith ◽  
...  

2019 ◽  
Vol 85 (21) ◽  
Author(s):  
Samat Amat ◽  
Edouard Timsit ◽  
Danica Baines ◽  
Jay Yanke ◽  
Trevor W. Alexander

ABSTRACT Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in beef cattle. Recent evidence suggests that commensal bacteria of the bovine nasopharynx have an important role in maintaining respiratory health by providing colonization resistance against pathogens. The objective of this study was to screen and select bacterial therapeutic candidates from the nasopharynxes of feedlot cattle to mitigate the BRD pathogen Mannheimia haemolytica. In a stepwise approach, bacteria (n = 300) isolated from the nasopharynxes of 100 healthy feedlot cattle were identified and initially screened (n = 178 isolates from 12 different genera) for growth inhibition of M. haemolytica. Subsequently, selected isolates were evaluated for the ability to adhere to bovine turbinate (BT) cells (n = 47), compete against M. haemolytica for BT cell adherence (n = 15), and modulate gene expression in BT cells (n = 10). Lactobacillus strains had the strongest inhibition of M. haemolytica, with 88% of the isolates (n =33) having inhibition zones ranging from 17 to 23 mm. Adherence to BT cells ranged from 3.4 to 8.0 log10 CFU per 105 BT cells. All the isolates tested in competition assays reduced M. haemolytica adherence to BT cells (32% to 78%). Among 84 bovine genes evaluated, selected isolates upregulated expression of interleukin 8 (IL-8) and IL-6 (P < 0.05). After ranking isolates for greatest inhibition, adhesion, competition, and immunomodulation properties, 6 Lactobacillus strains from 4 different species were selected as the best candidates for further development as intranasal bacterial therapeutics to mitigate M. haemolytica infection in feedlot cattle. IMPORTANCE Bovine respiratory disease (BRD) is a significant animal health issue impacting the beef industry. Current BRD prevention strategies rely mainly on metaphylactic use of antimicrobials when cattle enter feedlots. However, a recent increase in BRD-associated bacterial pathogens that are resistant to metaphylactic antimicrobials highlights a pressing need for the development of novel mitigation strategies. Based upon previous research showing the importance of respiratory commensal bacteria in protecting against bronchopneumonia, this study aimed to develop bacterial therapeutics that could be used to mitigate the BRD pathogen Mannheimia haemolytica. Bacteria isolated from the respiratory tracts of healthy cattle were characterized for their inhibitory, adhesive, and immunomodulatory properties. In total, 6 strains were identified as having the best properties for use as intranasal therapeutics to inhibit M. haemolytica. If successful in vivo, these strains offer an alternative to metaphylactic antimicrobial use in feedlot cattle for mitigating BRD.


2017 ◽  
Vol 41 ◽  
pp. 294-301
Author(s):  
José Luis RODRÍGUEZ-CASTILLO ◽  
Gilberto LÓPEZ-VALENCIA ◽  
Francisco Javier MONGE-NAVARRO ◽  
Gerardo Enrique MEDINA-BASULTO ◽  
Sawako HORI-OSHIMA ◽  
...  

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