Vaccination Against Poly-N-Acetylglucosamine Decreases Neutrophil Activation and Gvhd While Maintaining Microbial Diversity

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative therapy for different malignant and non-malignant hematologic diseases. Major life-threatening complications after allo-HCT are acute graft-versus-host disease (aGVHD) and severe infections. The incidence of GVHD after allo-HCT remains high, despite prophylactic immunosuppressive medication. According to the CIBMTR database, 60% of patients undergoing allo-HCT develop at least grade II-IV aGVHD. Microbial invasion into the intestinal mucosa after allo-HCT triggers the activation of neutrophil granulocytes (neutrophils) and requires antibiotic treatment to prevent sepsis. However, antibiotics lead to a loss of microbial diversity, which is connected to a higher incidence of aGVHD. Anti-microbial therapies which eliminate invading bacteria and diminish neutrophil-mediated damage without reducing the diversity of the microbiota are therefore highly desirable. A potential solution for this could be the use of anti-microbial antibodies that target and mark invading pathogens resulting in their elimination by innate immune cells. Therefore we investigated the potency of both active and passive immunization against the conserved microbial surface polysaccharide Poly-N-acetylglucosamine (PNAG) which is expressed on various pathogens in a murine aGVHD model. We could detect reduced aGVHD related mortality in mice which underwent treatment with an antibody against PNAG (anti-PNAG) or were actively immunized against PNAG. Sequencing analysis of the microbiota before and after allo-HCT showed that anti-PNAG treatment did not have any effect luminal microbial diversity. Mechanistically, we could show that anti-PNAG antibody treatment caused more abundant neutrophil recruitment to the intestinal submucosa. This supports the concept that neutrophils are able to effectively eliminate any opsonized bacteria in this tissue, leading to reduced local inflammation. In agreement with this we observed lower intestinal inflammation and reduced myeloperoxidase activity as well as proliferation of neutrophils in the small intestine of mice treated with anti-PNAG antibody. We demonstrate the potency of targeting PNAG as a novel antimicrobial treatment option in aGVHD by reducing uncontrolled neutrophil activation and thereby interfering with aGVHD without affecting commensal intestinal microbial diversity. Anti-PNAG-antibodies enhance anti-microbial immunity, while reducing the activation of neutrophil-mediated downstream immunopathology which is a novel approach to reduce the severity of GVHD. This could be translated into a clinical application given the modest toxicity profile of vaccination and the availability of fully human anti-PNAG antibodies, both of which have been tested in phase 1 trials in humans (ClinicalTrials.gov Identifier: NCT02853617). Disclosures Cywes-Bentley: OneBiopharma, Inc.: Honoraria. Koenecke:Novartis: Other: none. Pier:OneBiopharma, Inc.: Equity Ownership, Honoraria; Alopexx Vaccine, LLC: Equity Ownership, Honoraria.

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Immunization against poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1908549116 ◽

2019 ◽

Vol 116 (41) ◽

pp. 20700-20706 ◽

Cited By ~ 6

Author(s):

Jan Hülsdünker ◽

Oliver S. Thomas ◽

Eileen Haring ◽

Susanne Unger ◽

Nicolás Gonzalo Núñez ◽

...

Keyword(s):

Microbial Diversity ◽

Hematopoietic Cell Transplantation ◽

Polyclonal Antibodies ◽

Passive Immunization ◽

Neutrophil Activation ◽

Neutrophil Granulocytes ◽

Microbial Invasion ◽

Novel Approach ◽

Surface Polysaccharide

Microbial invasion into the intestinal mucosa after allogeneic hematopoietic cell transplantation (allo-HCT) triggers neutrophil activation and requires antibiotic interventions to prevent sepsis. However, antibiotics lead to a loss of microbiota diversity, which is connected to a higher incidence of acute graft-versus-host disease (aGVHD). Antimicrobial therapies that eliminate invading bacteria and reduce neutrophil-mediated damage without reducing the diversity of the microbiota are therefore highly desirable. A potential solution would be the use of antimicrobial antibodies that target invading pathogens, ultimately leading to their elimination by innate immune cells. In a mouse model of aGVHD, we investigated the potency of active and passive immunization against the conserved microbial surface polysaccharide poly-N-acetylglucosamine (PNAG) that is expressed on numerous pathogens. Treatment with monoclonal or polyclonal antibodies to PNAG (anti-PNAG) or vaccination against PNAG reduced aGVHD-related mortality. Anti-PNAG treatment did not change the intestinal microbial diversity as determined by 16S ribosomal DNA sequencing. Anti-PNAG treatment reduced myeloperoxidase activation and proliferation of neutrophil granulocytes (neutrophils) in the ileum of mice developing GVHD. In vitro, anti-PNAG treatment showed high antimicrobial activity. The functional role of neutrophils was confirmed by using neutrophil-deficient LysMcreMcl1fl/fl mice that had no survival advantage under anti-PNAG treatment. In summary, the control of invading bacteria by anti-PNAG treatment could be a novel approach to reduce the uncontrolled neutrophil activation that promotes early GVHD and opens a new avenue to interfere with aGVHD without affecting commensal intestinal microbial diversity.

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RNA sequencing analysis of activated macrophages treated with the anti-HIV ABX464 in intestinal inflammation

Scientific Data ◽

10.1038/sdata.2017.150 ◽

2017 ◽

Vol 4 (1) ◽

Cited By ~ 2

Author(s):

Laurent Manchon ◽

Karim Chebli ◽

Laura Papon ◽

Conception Paul ◽

Aude Garcel ◽

...

Keyword(s):

Rna Sequencing ◽

Intestinal Inflammation ◽

Sequencing Analysis ◽

Activated Macrophages ◽

Anti Hiv

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Intestinal Anti-Inflammatory Activity of the Aqueous Extract from Ipomoea asarifolia in DNBS-Induced Colitis in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms19124016 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4016 ◽

Cited By ~ 9

Author(s):

Valéria da Silva ◽

Aurigena de Araújo ◽

Daline Araújo ◽

Maíra Lima ◽

Roseane Vasconcelos ◽

...

Keyword(s):

Protective Effect ◽

Aqueous Extract ◽

Intestinal Inflammation ◽

Activity Index ◽

Immunohistochemical Analysis ◽

Histological Evaluation ◽

Myeloperoxidase Activity ◽

Down Regulation ◽

Anti Inflammatory ◽

Ipomoea Asarifolia

Inflammatory bowel disease is triggered by an uncontrolled immune response associated with genetic, environmental, and intestinal microbiota imbalance. Ipomoea asarifolia (IA), popularly known as “salsa” or “brave salsa”, belongs to the Convolvulaceae family. The aim of this approach was to study the preventive effect of IA aqueous extract in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats. Rats pretreated with IA extract or sulfasalazine (SSZ) received intracolonic instillation of DNBS in 50% ethanol (v/v). IA extract presented a protective effect against intestinal inflammation, with improvement in the disease activity index and macroscopic damage. IA or SSZ significantly reduced myeloperoxidase activity, and also down-regulation of the gene expression of JNK1, NF-κβ-p65, STAT3, and decreased levels of TNFα, IL-1β, and increased IL-10, associated with a significant improvement of oxidative stress, in addition to a reduction in MDA and an increase of glutathione in colonic tissue. The protective effect of the extract was also confirmed in histological evaluation, showing preservation of the colonic cytoarchitecture. Immunohistochemical analysis revealed down-regulation of NF-κβ-p65, iNOS, IL-17, and up-regulation of SOCs-1 and MUC-2. IA extract presents antioxidant and anti-inflammatory intestinal properties, and proved to be a potential application for preventing damage induced by DNBS.

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Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00248.2018 ◽

2019 ◽

Vol 316 (6) ◽

pp. G692-G700 ◽

Cited By ~ 6

Author(s):

Emmeline Salameh ◽

Mathieu Meleine ◽

Guillaume Gourcerol ◽

Jean-Claude do Rego ◽

Jean-Luc do Rego ◽

...

Keyword(s):

Intestinal Inflammation ◽

Visceral Pain ◽

Myeloperoxidase Activity ◽

Therapeutic Approaches ◽

Chronic Colitis ◽

Functional Symptoms ◽

Tnf Α ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Novel Therapeutic

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15–45 mg of TNBS) in 30 rats, whereas the control rats ( n = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced 1) a visceral hypersensitivity ( P = 0.03), 2) an increased colon weight-to-length ratio ( P = 0.01), 3) higher inflammatory and fibrosis scores ( P = 0.0390 and P = 0.0016, respectively), and 4) a higher colonic IL-6 and IL-10 production ( P = 0.008 and P = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae.NEW & NOTEWORTHY Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in the remission period. It might define novel therapeutic approaches to achieve a better inflammatory bowel disease-related sequelae management.

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Deletion of neutral endopeptidase exacerbates intestinal inflammation induced by Clostridium difficiletoxin A

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.2.g544 ◽

2001 ◽

Vol 281 (2) ◽

pp. G544-G551 ◽

Cited By ~ 33

Author(s):

Kimberly S. Kirkwood ◽

Nigel W. Bunnett ◽

John Maa ◽

Ignazio Castagliolo ◽

Bao Liu ◽

...

Keyword(s):

Acute Inflammation ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Fluid Secretion ◽

Neutral Endopeptidase ◽

Myeloperoxidase Activity ◽

Wild Type ◽

Neutrophil Accumulation ◽

Genetic Deletion ◽

Neurokinin 1

Toxin A (TxA) of Clostridium difficile induces acute inflammation of the intestine initiated by release of substance P (SP) and activation of the neurokinin-1 receptor. However, the mechanisms that terminate this response are unknown. We determined whether the SP-degrading enzyme neutral endopeptidase (NEP, EC 3.4.24.11 ) terminates TxA-induced enteritis. We used both genetic deletion and pharmacological inhibition of NEP to test this hypothesis. In wild-type mice, instillation of TxA (0.5–5 μg) into ileal loops for 3 h dose dependently increased ileal fluid secretion, stimulated granulocyte transmigration determined by myeloperoxidase activity, and caused histological damage characterized by depletion of enterocytes, edema, and neutrophil accumulation. Deletion of NEP reduced the threshold secretory and inflammatory dose of TxA and exacerbated the inflammatory responses by more than twofold. This exacerbated inflammation was prevented by pretreatment with recombinant NEP. Conversely, pretreatment of wild-type mice with the NEP inhibitor phosphoramidon exacerbated enteritis. Thus NEP terminates enteritis induced by C. difficile TxA, underlying the importance of SP degradation in limiting neurogenic inflammation.

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Fruit Consumption is Associated with Alterations in Microbial Composition and Lower Rates of Pouchitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz053 ◽

2019 ◽

Vol 13 (10) ◽

pp. 1265-1272 ◽

Cited By ~ 7

Author(s):

L Godny ◽

N Maharshak ◽

L Reshef ◽

I Goren ◽

L Yahav ◽

...

Keyword(s):

Microbial Diversity ◽

Intestinal Inflammation ◽

Disease Recurrence ◽

Rrna Gene ◽

Microbial Composition ◽

Fruit Consumption ◽

Entire Cohort ◽

Faecal Samples ◽

16S Rrna Gene Pyrosequencing ◽

Microbial Analysis

Abstract Background Patients with ulcerative colitis [UC] who undergo proctocolectomy with an ileal pouch–anal anastomosis commonly develop pouch inflammation [pouchitis]. Pouchitis develops in a previously normal small intestine and may involve environmental factors. We explored whether diet and microbiota alterations contributed to the pathogenesis of pouchitis. Methods Patients were recruited and prospectively followed at a comprehensive pouch clinic. Pouch behaviour was clinically defined as a normal pouch [NP] or pouchitis. Patients completed Food Frequency Questionnaires [FFQs]. Faecal samples were analysed for microbial composition [16S rRNA gene pyrosequencing]. Results Nutritional evaluation was performed in 172 patients [59% females], and of these, faecal microbial analysis was performed in 75 patients (microbiota cohort: NP [n = 22], pouchitis [n = 53]). Of the entire cohort, a subgroup of 39 [22.6%] patients had NP at recruitment [NP cohort]. Of these, 5 [12.8%] developed pouchitis within a year. Patients at the lowest tertile of fruit consumption [<1.45 servings/day] had higher rates of pouchitis compared with those with higher consumption [30.8% vs 3.8%, log rank, p = 0.03]. Fruit consumption was correlated with microbial diversity [r = 0.35, p = 0.002] and with the abundance of several microbial genera, including Faecalibacterium [r = 0.29, p = 0.01], Lachnospira [r = 0.38, p = 0.001], and a previously uncharacterized genus from the Ruminococcaceae family [r = 0.25, p = 0.05]. Reduction in fruit consumption over time was associated with disease recurrence and with reduced microbial diversity [Δ = –0.8 ± 0.3, p = 0.008]. Conclusions Fruit consumption is associated with modification of microbial composition, and lower consumption was correlated with the development of pouchitis. Thus, fruit consumption may protect against intestinal inflammation via alteration of microbial composition.

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Factor XI Inhibitor Antibody Treatment Improves Survival In a Murine Polymicrobial Sepsis Model

Blood ◽

10.1182/blood.v116.21.820.820 ◽

2010 ◽

Vol 116 (21) ◽

pp. 820-820

Author(s):

Erik I Tucker ◽

Melani Helm ◽

Owen JT McCarty ◽

Sawan Hurst ◽

David Gailani ◽

...

Keyword(s):

Protein C ◽

Cecal Ligation ◽

Polymicrobial Sepsis ◽

Human Populations ◽

Factor Xi ◽

Antibody Treatment ◽

Intravascular Coagulation ◽

Consumptive Coagulopathy ◽

Sepsis Model ◽

Equity Ownership

Abstract Abstract 820 Sepsis results in a systemic inflammatory state that is frequently accompanied by intravascular coagulation and fibrinolysis, resulting in a coagulopathy with thrombotic and hemorrhagic components (disseminated intravascular coagulation– DIC). We have shown that the plasma coagulation protease factor XI (FXI) contributes substantially to experimental thrombus formation in baboons and mice, but does not appear to be essential for hemostasis. These results are supported by studies in human populations that show FXI deficiency confers a decreased risk of thrombotic ischemic stroke and deep venous thrombosis, while the associated bleeding diathesis is often mild. FXI appears to contribute to lethal consumptive coagulopathy in protein C deficient mice, while FXI deficiency reduces DIC and prolongs survival of surgical cecal-ligation and puncture (CLP)-induced abdominal sepsis in mice. Taken together, these data suggest that FXI may be an important contributor to the response leading to DIC in sepsis, and that inhibiting FXI may be a safer therapeutic alternative in this setting to activated protein C (APC), which can exacerbate hemorrhage. To investigate the contribution of FXI to consumptive coagulopathy and mortality in sepsis we used the standard CLP polymicrobial sepsis model. To inhibit FXI in the mouse, we developed a new murine anti-mouse FXI monoclonal antibody (14E11) that targets the Apple 2 domain of FXI, and has been shown in vitro to inhibit the activation of FXI by factor XIIa, while not significantly inhibiting activation by thrombin. A single injection of 14E11 (4 mg/kg, SC) prolonged the aPTT of mice up to 3-fold for 48 hrs. Following CLP, the abdomen was closed and mice were treated with vehicle (PBS, SC), APC (6 mg/kg, SC), or 14E11 (4 mg/kg, SC) (n=20 for each group). Overall survival was 45% for vehicle, 15% for APC, and 80% for 14E11 treated mice (P<0.001 for 14E11 vs. both APC and vehicle). 24 hrs after CLP, platelet count in vehicle, APC, and 14E11 treated mice (n=8 each) were lower by 24±7%, 25±5%, and 12±6%, and leukocyte counts were lower by 51±15%, 42±14%, and 43±13% respectively, compared with baseline. Thrombin/antithrombin complex levels were higher in the vehicle treated group 24 hrs after CLP (5.0±1.2 μg/L) compared with 2.2±0.2 μg/L in normal healthy mice (P<0.05), while APC and 14E11 treated groups showed only moderately elevated TAT levels (2.6±0.2 and 2.7±0.4 μg/L, respectively). The pharmacological effects of 14E11 later in the course of sepsis and the apparent poor outcome of early APC treatment remain to be evaluated. In a separate cohort (n=12 each), tail-clip bleeding times were 12.8±1.0, 17.9±1.8, and 12.1±1.7 min for vehicle, APC, and 14E11 treated animals respectively (P<0.05 for APC vs. vehicle and 14E11) 30min after injection. In summary, the outcome was better for 14E11 treated mice in CLP-induced sepsis compared to vehicle or APC treatment, and the data indicate that consumptive coagulopathy may be less severe following FXI inhibition. Furthermore, mice treated with 14E11 showed no increase in bleeding compared with vehicle treatment, while APC significantly prolonged the tail bleeding time. The results suggest that therapeutic inhibition of FXI, by specifically inhibiting FXI activation by FXIIa, could be beneficial in treating sepsis-related DIC. It is also possible that inhibition of FXI may limit DIC with a lower risk of exacerbating bleeding when compared to anticoagulant therapies such as heparin or APC. Disclosures: Tucker: Aronora,LLC: Employment, Equity Ownership, Patents & Royalties. Helm:Aronora,LLC: Employment. Gruber:Aronora,LLC: Consultancy, Equity Ownership, Patents & Royalties.

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Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00019-09 ◽

2009 ◽

Vol 16 (5) ◽

pp. 660-666 ◽

Cited By ~ 49

Author(s):

Monisha Dhiman ◽

Jose Guillermo Estrada-Franco ◽

Jasmine M. Pando ◽

Francisco J. Ramirez-Aguilar ◽

Heidi Spratt ◽

...

Keyword(s):

Chagas Disease ◽

Nitrosative Stress ◽

Hypochlorous Acid ◽

Inflammatory Responses ◽

Neutrophil Activation ◽

Enzyme Linked Immunosorbent Assay ◽

No Production ◽

Myeloperoxidase Activity ◽

Protein Nitration ◽

Specific Antibodies

ABSTRACT In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitrotyrosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (O2 − source) and nitrate/nitrite contents (denotes iNOS activation and NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological NO and O2 − concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies capable of suppressing MPO activity may be useful in controlling the inflammation and oxidative/nitrosative pathology in chagasic cardiomyopathy.

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Nitecapone Reduces Cardiac Neutrophil Accumulation in Clinical Open Heart Surgery

Anesthesiology ◽

10.1097/00000542-199908000-00007 ◽

1999 ◽

Vol 91 (2) ◽

pp. 355-361 ◽

Cited By ~ 6

Author(s):

Eero J. Pesonen ◽

Antti E. Vento ◽

Juhani O. Ramo ◽

Juha Vuorte ◽

Sten-Erik Jansson ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Cardiopulmonary Bypass ◽

Stroke Volume ◽

Left Ventricular ◽

Neutrophil Activation ◽

Myeloperoxidase Activity ◽

Left Ventricular Stroke Volume ◽

Neutrophil Accumulation ◽

Hydrogen Peroxide Production ◽

Ventricular Stroke Volume

Background To study the effect of nitecapone, a novel antioxidant, on cardiac neutrophil activation during cardiopulmonary bypass in patients. Methods In a double-blind, placebo controlled trial, 30 male patients undergoing coronary artery bypass grafting were randomly assigned to control (crystalloid cardioplegia, n = 15) and nitecapone groups (cardioplegia supplemented with nitecapone, n = 15). Leukocyte differential counts, neutrophil and monocyte CD11b and L-selectin expressions and neutrophil hydrogen peroxide production were measured in blood samples parallelly obtained from the coronary sinus and aorta before cardiopulmonary bypass and at 1, 5, and 10 min after aortic declamping. Myocardial myeloperoxidase activity was analyzed in biopsies taken at 1, 5, and 10 min after declamping. Results Transcoronary neutrophil difference (i.e., aorta--sinus coronarius) at 1 min after aortic declamping was significantly lower in nitecapone-treated patients (0.41 [-0.42-0.98] x 10(9) cells/l) than in controls (0.68 [-0.28-2.47] x 10(9) cells/l; P = 0.032). At 5 min after aortic declamping, significant transcoronary reduction of neutrophil hydrogen peroxide production and CD11b expression were observed in controls but not in nitecapone patients. At 24 h postoperatively, left ventricular stroke volume was better in nitecapone-treated patients (94 [51-118] ml) than controls (66 [40-104] ml; P= 0.018). Data are median [range]. Conclusion Nitecapone added to cardioplegia solution reduces cardiac neutrophil accumulation and transcoronary neutrophil activation during clinical cardiopulmonary bypass. Reflected by better left ventricular stroke volume, nitecapone treatment may be an additional way of reducing the deleterious effects of neutrophil activation during cardiopulmonary bypass.

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Rumen microbial diversity under influence of a polyclonal antibody preparation against lactate-producing and proteolytic bacteria in cows fed different energy sources

Revista Brasileira de Saúde e Produção Animal ◽

10.1590/s1519-99402012000200017 ◽

2012 ◽

Vol 13 (2) ◽

pp. 491-502 ◽

Cited By ~ 3

Author(s):

Walter Guimarães Otero ◽

Carolina Tobias Marino ◽

Cristine Chaves Barreto ◽

Vivian Helena Pellizari ◽

Danilo Domingues Millen ◽

...

Keyword(s):

Microbial Diversity ◽

Polyclonal Antibody ◽

Passive Immunization ◽

Latin Squares ◽

Feed Additives ◽

Community Diversity ◽

Feed Additive ◽

Energy Sources ◽

Antibody Preparation ◽

Citrus Pulp

Nine ruminally cannulated cows fed different energy sources were used to evaluate an avianderived polyclonal antibody preparation against specific ruminal bacteria and monensin on microbial community diversity. The experimental design was three Latin squares 3 x 3 distinguished by the main energy source in the diet [dry-ground corn grain, high moisture corn silage or citrus pulp]. Inside each Latin square, animals received one of the feed additives per period [control, monensin or polyclonal antibody preparation]. Each period lasted 21 days where 20 were used for treatments adaptation and the last one for sampling collection. Microbial diversity was evaluated by protozoa counts and denaturing gradient gel electrophoresis. Polyclonal antibodies plus citrus pulp (CiPu) addition in the diet resulted in an increase of relative counting of Isotricha protozoa that indicates a possible effect on this ruminal ciliate population. In general lines, in the present experiment, it was not possible to assign that there was a pattern in the structures of amplification of Bacteria and Archaea communities of the ruminal content. Oral passive immunization is a technology that arises as an effective alternative for feed additive production. Further research is still necessary to better understand its mechanisms of action.

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