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Ahmed Elmoslemany - One of the best experts on this subject based on the ideXlab platform.

  • The diagnostic accuracy of oxidative stress biomarkers in sheep with Pneumonic Pasteurellosis
    Comparative Clinical Pathology, 2017
    Co-Authors: Wael M. El-deeb, Ahmed Elmoslemany
    Abstract:

    The goal of this study was to decide the diagnostic accuracy of oxidative stress biomarkers in infected sheep with Pasteurella multocida. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Al-Ahsa region, Saudi Arabia. Serum samples were evaluated for oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT)). Additionally, nasal swabs and bronchoalveolar lavages were gathered from all sheep for bacteriological investigations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. The results showed significantly higher MDA level and lower SOD, GSH and CAT levels in Pneumonic sheep compared to healthy controls. Both MDA and CAT showed the highest positive ( r  = 0.72) and negative ( r  = −0.71) correlation with disease status, respectively. Finally, MDA showed a relatively better test characteristic than other parameters, with an area under the curve (AUC = 0.93) indicating high degree of discrimination between control and Pneumonic sheep. Conclusively, this study shed the light on the value of oxidative stress biomarkers in the diagnosis of naturally occurring Pneumonic Pasteurellosis in sheep.

  • the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with Pneumonic Pasteurellosis
    PeerJ, 2016
    Co-Authors: Wael M Eldeeb, Ahmed Elmoslemany
    Abstract:

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with Pneumonic Pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring Pneumonic Pasteurellosis in sheep.

Wael M Eldeeb - One of the best experts on this subject based on the ideXlab platform.

  • the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with Pneumonic Pasteurellosis
    PeerJ, 2016
    Co-Authors: Wael M Eldeeb, Ahmed Elmoslemany
    Abstract:

    The goal of this study was to assess the diagnostic accuracy of acute phase proteins and proinflammatory cytokines in sheep with Pneumonic Pasteurellosis. Blood samples were collected from 56 sheep (36 naturally infected with Pasteurella multocida and 20 healthy controls) belonging to one farm in Eastern region, Saudi Arabia. Serum samples were evaluated for acute phase proteins (Haptoglobin (Hp), serum amyloid A (SAA) and fibrinogen (Fb)), and the proinflammatory cytokines (interleukins (IL-1α, IL-1β, and IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-ϒ)). Additionally, nasopharyngeal swabs and bronchoalveolar lavages were collected from all animals for bacteriological examinations. Receiver operating characteristic curve was used to assess the diagnostic performance of each parameter. All parameters showed moderate to high degree of positive correlation with case-control status. There was no significant difference in the area under the curve (AUC) among acute phase proteins; however, both Hp and SAA showed better sensitivity and specificity than Fb. The proinflammatory cytokines (IL1-α, IL1-β, and IL6) showed similar and highly accurate diagnostic performance (AUC > 0.9), whereas IFN-ϒ was moderately accurate (AUC = 0.79). In conclusion, this study confirms the value of acute phase proteins and cytokines as diagnostic biomarkers of naturally occuring Pneumonic Pasteurellosis in sheep.

  • lipoproteins profile acute phase proteins proinflammatory cytokines and oxidative stress biomarkers in sheep with Pneumonic Pasteurellosis
    Comparative Haematology International, 2015
    Co-Authors: Wael M Eldeeb, Mohamed Tharwat
    Abstract:

    The aim of this study was to assess the pathophysiological importance of lipid profile, acute phase proteins, proinflammatory cytokines and oxidative stress markers in sheep with Pneumonic Pasteurellosis. Blood samples were collected from 36 Pasteurella multocida-infected sheep, together with 20 healthy controls. Samples for bacteriological examination (nasal swabs, bronchoalveolar lavage) were collected from all animals and subjected to bacteriological examinations. Moreover, heart blood and lung samples were collected from the dead Pneumonic sheep and subjected also to bacteriological examinations. A lipid profile was determined, along with a blood picture and other biochemical parameters. The acute phase proteins (fibrinogen, haptoglobin, serum amyloid A), the proinflammatory cytokine tumour necrosis factor-alpha, interleukins (IL-1α, IL-1β, IL-6), interferon-gamma and the oxidative stress markers malondialdehyde, super oxide dismutase, glutathione and catalase were also measured. The examined biochemical parameters were increased in the Pneumonic sheep, except for cholesterol and high-density lipoprotein cholesterol (HDL-c), which were significantly lower than control group. Acute phase proteins and cytokines were significantly higher in the Pneumonic sheep when compared to the healthy sheep. There was a significant increase in the levels of malondialdehyde; however, a significant decrease in the levels of super oxide dismutase, glutathione and catalase was observed. The present study shed the light on the possible pathphysiological role of lipid profile, acute phase proteins (APPs), proinflammatory cytokines and oxidative stress markers in Pneumonic pasteurelosis in sheep.

S K Maheswaran - One of the best experts on this subject based on the ideXlab platform.

  • construction of an isogenic leukotoxin deletion mutant of pasteurella haemolytica serotype 1 characterization and virulence
    Microbial Pathogenesis, 1998
    Co-Authors: Fred M Tatum, Srinand Sreevatsan, Robert E Briggs, Emile S Zehr, Shihling Hsuan, Laurence O Whiteley, Trevor R Ames, S K Maheswaran
    Abstract:

    Allelic replacement was used to generate two isogenic lktA deletion mutants of Pasteurella haemolytica serotype 1 that were incapable of synthesizing leukotoxin (Lkt). Southern blot data confirmed that lktA sequences were absent in the two P. haemolytica deletion mutants. Culture supernatants and whole cell lysates from the wild type P. haemolytica, D153 parent strain, but not the lktA deletion mutants, contained immunoreactive and bioactive leukotoxic protein. In addition, only the parent strain was haemolytic when grown on bovine and sheep blood agar plates. Virulence of the lktA deletion mutant, lktA 77, was compared with the parent in an experimentally infected calf model of Pneumonic Pasteurellosis. Results revealed significant reduction in virulence in the lktA mutant as measured by clinical and lung lesion scores. Notable differences in histological changes such as markedly reduced necrosis and lack of leukocyte degeneration occurred in calves infected with the lktA mutant in comparison with those infected with the parent wild-type strain. Thus, it appears that leukotoxin plays a important role in the pathogenesis of lung injury in bovine Pneumonic Pasteurellosis.

  • evaluation of efficacy of three commercial vaccines against experimental bovine Pneumonic Pasteurellosis
    Veterinary Microbiology, 1996
    Co-Authors: S Srinand, S K Maheswaran, Trevor R Ames, Ronald E Werdin, Shihling Hsuan
    Abstract:

    The objective of this study was to evaluate the efficacy of three commercial vaccines against experimental Pneumonic Pasteurellosis in cattle. The three vaccines were: (a) One Shot (SmithK-line Beecham, West Chester, PA.), (b) Presponse (Langford Laboratories, Guelph, Ontario) and (c) Once PMH (BioCor, Omaha, NE.). Protective immunity was evaluated in terms of lower clinical and Pneumonic lesion scores after endobronchial challenge with virulent P. haemolytica. The results indicate that One Shot elicited antibodies against leukotoxin (Lkt), capsular polysaccharide (CP) and surface antigens (SA), while Presponse and Once PMH elicited antibodies against CP and SA. There was significant correlation between lung and serum antibody levels against Lkt (P < 0.0001), CP (P ≤ 0.0001) and IROMPs (P ≤ 0.035). Animals that received the One Shot had significantly (P ≤ 0.05) lower mean Pneumonic lesion score (36.6 ± 10.97) as compared to the control group (48.6 ± 25.92). A significant negative correlation (−0.41; P ≤ 0.008) existed between serum antibody levels against Lkt and Pneumonic lesion score. High serum antibodies against SA did not correlate with reduction in Pneumonic lesion score. In addition, high antibody levels against CP did not correlate consistently with reduced Pneumonic lesion scores. The results from this study demonstrates that commercial vaccines evaluated in this trial did not confer optimal protection in vaccinated calves, against experimental Pneumonic Pasteurellosis. However, One Shot vaccinates showed a better protective immunity compared to the other two vaccine groups.

  • evaluation of three experimental subunit vaccines against Pneumonic Pasteurellosis in cattle
    Vaccine, 1996
    Co-Authors: Srinand Sreevatsan, Trevor R Ames, Ronald E Werdin, Han Sang Yoo, S K Maheswaran
    Abstract:

    The objective of this study was to evaluate the efficacy of three Pasteurella haemolytica A1 derived experimental subunit vaccines against Pneumonic Pasteurellosis in cattle. The three vaccines were: (a) culture supernatant (CS) containing leukotoxin (Lkt), lipopolysaccharide (LPS) and capsular polysaccharide (CP); (b) sodium salicylate extract (SSE) containing iron regulated outer membrane proteins (IROMPs), LPS and CP; (c) and a combination of the above two. Vaccine efficacy was defined in terms of reduction in clinical and Pneumonic lesion scores after intrapulmonic challenge with live P. haemolytica. The results indicate that the CS vaccine elicited antibodies against both Lkt and CP, while the SSE vaccine elicited antibodies against IROMPs and CP. Animals inoculated with the combination vaccine showed increased levels of antibodies against IROMPs, Lkt and CP. There was significant correlation between lung and serum antibodies against Lkt, CP and IROMPs. Animals that received the combination vaccine had significantly lower mean Pneumonic lung score as compared to SSE and control groups. The animals which received CS vaccine had mean Pneumonic lung score significantly lower than that of control group. A strong negative correlation existed between serum antibody levels against Lkt, IROMPs, CP and Pneumonic lung scores. The results from this study demonstrate the usefulness of CS vaccine alone or in combination with SSE vaccine in bringing about optimal protection in vaccinated calves, against experimental Pneumonic Pasteurellosis.

  • increased tumor necrosis factor α and interleukin 1β expression in the lungs of calves with experimental Pneumonic Pasteurellosis
    Veterinary Immunology and Immunopathology, 1995
    Co-Authors: Han Sang Yoo, S K Maheswaran, Trevor R Ames, S Srinand, M Suresh
    Abstract:

    Abstract We used a well characterized Pneumonic Pasteurellosis model in calves to determine whether increased proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression and secretion were associated with Pneumonic lesions. Bronchoalveolar lavage fluids, lavage cells consisting of alveolar macrophages and neutrophils with degenerative changes, and lung tissues were analyzed for the presence of TNF-α and IL-1β approximately 48 h following endobronchial inoculation of logarithmic phase Pasteurella haemolytica 12296 organisms. Levels of TNF-α and IL-1β mRNA were significantly increased in lavage cells of P. haemolytica-infected animals but not in cells from phosphate buffered saline (PBS) inoculated controls based on in situ hybridization analysis. Significantly increased levels of TNF-α, and IL-1β mRNA were also expressed within the Pneumonic lesions from P. haemolytica-infected calves. In contrast, lung tissues from PBS-inoculated control calves had cytokine mRNAs expressed at extremely low levels. Increased levels of bioactive IL-1 and immunoreactive (not bioactive) TNF-α were found in lavage fluids from P. haemolytica-infected calves compared with lavage fluids from PBS-inoculated calves. These findings indicate that the proinflammatory cytokines TNF-α and IL-1, may be associated with pathogenesis of lung injury in bovine Pneumonic Pasteurellosis.

  • efficacy of various vaccines against Pneumonic Pasteurellosis in cattle a meta analysis
    Preventive Veterinary Medicine, 1995
    Co-Authors: S Srinand, S K Maheswaran, Trevor R Ames, Vickie L King
    Abstract:

    The objective of this study was to compare the protective efficacy induced by various experimental and commercial vaccines used in the past 12 years (1982–1994) against bovine Pneumonic Pasteurellosis. All studies using an experimental-challenge model to evaluate protective efficacy induced by vaccine preparations were identified using a combination of VETCD, CAB, and MEDLINE searches. A total of 72 trials were identified in 27 studies. Age groups of animals used, sample sizes used, vaccine types, route of vaccination, dose of vaccine, adjuvant types, booster times, time of challenge since first vaccination, challenge methods, challenge doses, challenge route, observation times postchallenge, and raw mean lung-lesion scores (defined as percent lung involved) were extracted from each publication and used in the analysis. Vaccine types were grouped into 11 categories as controls, live, potassium thiocyanate (KSCN) extract, phosphate buffered saline extract (PBSE), 30 kDa recombinant protein, bacterin, streptomycin dependent live (SmD live), sodium salicylate extract (SSE), sarkosyl outer membrane protein extract (sarkosyl OMP), or culture supernatant (CS) categories based on the subunit content in each preparation. In a second analysis, the chemically altered live vaccine was grouped together with live SmD group as modified live vaccines. The leastsquares means of the postchallenge lung-lesion scores of each vaccine type were then compared after controlling for all the above-mentioned variables in an analysis of variance using Fischer's protected least significant difference. The statistical analysis was done using the general linear models procedure of Statistical Analysis Systems Institute Inc.. Protective indices for each vaccine type were calculated as a function of independent probabilities of protection among vaccinates and controls. The protective indices of each vaccine type were then compared in a similar model. Cattle vaccinated with live vaccines had the smallest lung-lesion scores (9 ± 8) which significantly differed from that of controls (44 ± 8), bacterins (23 ± 6), and live SmD (38 ± 12) or modified live (31 ± 10). KSCN extract (9 ± 10), bacterin, and CS (20 ± 9) also had significantly lower (P < 0.05) lung-lesion scores compared to controls. The CS and KSCN vaccines showed a significantly (P < 0.05) better protective index (PI) (0.70 and 0.68 respectively) than bacterins (0.50) or bacterin + CS (0.44) vaccines. Saline extract and live vaccines had better (P < 0.05) PI (0.60 and 0.70 respectively) compared to bacterins.

Trevor R Ames - One of the best experts on this subject based on the ideXlab platform.

  • pulmonary expression of tumor necrosis factor alpha interleukin 1 beta and interleukin 8 in the acute phase of bovine Pneumonic Pasteurellosis
    Veterinary Pathology, 2001
    Co-Authors: C Malazdrewich, Trevor R Ames, Mitchell S Abrahamsen, Shyamala Maheswaran
    Abstract:

    Inflammatory cytokines are suspected to contribute to the pathogenesis of bovine Pneumonic Pasteurellosis (BPP) through neutrophil recruitment, leukocyte activation, and the induction of a broad array of soluble inflammatory mediators. An in vivo experimental model of BPP was used to characterize the pulmonary expression kinetics of tumor necrosis factor alpha (TNF), interleukin-1 beta (IL-1), and interleukin-8 (IL-8) genes and proteins during the acute phase of disease development. Cytokine expression in bronchoalveolar lavage (BAL) fluid, BAL cells, and Pneumonic lung parenchyma was quantitated by northern blot analysis, enzyme-linked immunosorbent assay (ELISA), and in situ hybridization at 2, 4, 8, 16, and 24 hours after endobronchial inoculation of Pasteurella (Mannheimia) haemolytica. Expression of TNF ,I L-1, and IL-8 was significantly increased in the airways and lung lesions of infected calves as compared with mock-infected controls. Although kinetic patterns varied, peak levels of cytokine mRNA occurred within 8 hours postinfection (PI), and peak cytokine concentrations occurred within 16 hours PI. In all samples, IL-8 was expressed to the greatest extent and TNF was least expressed. Expression of TNF was restricted to alveolar macrophages. Alveolar and interstitial macrophages produced IL-1 and IL-8 in thefirst 4 hours; bronchial and bronchiolar epithelial cells were also significant sources of IL-8 during this period. By 8 hours PI, neutrophils were the dominant source of both IL-1 and IL-8. These findings demonstrate a spatial and temporal association between pulmonary expression of inflammatory cytokines and acute lung pathology, supporting the hypothesis that cytokines contribute to inflammatory lung injury in BPP.

  • construction of an isogenic leukotoxin deletion mutant of pasteurella haemolytica serotype 1 characterization and virulence
    Microbial Pathogenesis, 1998
    Co-Authors: Fred M Tatum, Srinand Sreevatsan, Robert E Briggs, Emile S Zehr, Shihling Hsuan, Laurence O Whiteley, Trevor R Ames, S K Maheswaran
    Abstract:

    Allelic replacement was used to generate two isogenic lktA deletion mutants of Pasteurella haemolytica serotype 1 that were incapable of synthesizing leukotoxin (Lkt). Southern blot data confirmed that lktA sequences were absent in the two P. haemolytica deletion mutants. Culture supernatants and whole cell lysates from the wild type P. haemolytica, D153 parent strain, but not the lktA deletion mutants, contained immunoreactive and bioactive leukotoxic protein. In addition, only the parent strain was haemolytic when grown on bovine and sheep blood agar plates. Virulence of the lktA deletion mutant, lktA 77, was compared with the parent in an experimentally infected calf model of Pneumonic Pasteurellosis. Results revealed significant reduction in virulence in the lktA mutant as measured by clinical and lung lesion scores. Notable differences in histological changes such as markedly reduced necrosis and lack of leukocyte degeneration occurred in calves infected with the lktA mutant in comparison with those infected with the parent wild-type strain. Thus, it appears that leukotoxin plays a important role in the pathogenesis of lung injury in bovine Pneumonic Pasteurellosis.

  • evaluation of efficacy of three commercial vaccines against experimental bovine Pneumonic Pasteurellosis
    Veterinary Microbiology, 1996
    Co-Authors: S Srinand, S K Maheswaran, Trevor R Ames, Ronald E Werdin, Shihling Hsuan
    Abstract:

    The objective of this study was to evaluate the efficacy of three commercial vaccines against experimental Pneumonic Pasteurellosis in cattle. The three vaccines were: (a) One Shot (SmithK-line Beecham, West Chester, PA.), (b) Presponse (Langford Laboratories, Guelph, Ontario) and (c) Once PMH (BioCor, Omaha, NE.). Protective immunity was evaluated in terms of lower clinical and Pneumonic lesion scores after endobronchial challenge with virulent P. haemolytica. The results indicate that One Shot elicited antibodies against leukotoxin (Lkt), capsular polysaccharide (CP) and surface antigens (SA), while Presponse and Once PMH elicited antibodies against CP and SA. There was significant correlation between lung and serum antibody levels against Lkt (P < 0.0001), CP (P ≤ 0.0001) and IROMPs (P ≤ 0.035). Animals that received the One Shot had significantly (P ≤ 0.05) lower mean Pneumonic lesion score (36.6 ± 10.97) as compared to the control group (48.6 ± 25.92). A significant negative correlation (−0.41; P ≤ 0.008) existed between serum antibody levels against Lkt and Pneumonic lesion score. High serum antibodies against SA did not correlate with reduction in Pneumonic lesion score. In addition, high antibody levels against CP did not correlate consistently with reduced Pneumonic lesion scores. The results from this study demonstrates that commercial vaccines evaluated in this trial did not confer optimal protection in vaccinated calves, against experimental Pneumonic Pasteurellosis. However, One Shot vaccinates showed a better protective immunity compared to the other two vaccine groups.

  • evaluation of three experimental subunit vaccines against Pneumonic Pasteurellosis in cattle
    Vaccine, 1996
    Co-Authors: Srinand Sreevatsan, Trevor R Ames, Ronald E Werdin, Han Sang Yoo, S K Maheswaran
    Abstract:

    The objective of this study was to evaluate the efficacy of three Pasteurella haemolytica A1 derived experimental subunit vaccines against Pneumonic Pasteurellosis in cattle. The three vaccines were: (a) culture supernatant (CS) containing leukotoxin (Lkt), lipopolysaccharide (LPS) and capsular polysaccharide (CP); (b) sodium salicylate extract (SSE) containing iron regulated outer membrane proteins (IROMPs), LPS and CP; (c) and a combination of the above two. Vaccine efficacy was defined in terms of reduction in clinical and Pneumonic lesion scores after intrapulmonic challenge with live P. haemolytica. The results indicate that the CS vaccine elicited antibodies against both Lkt and CP, while the SSE vaccine elicited antibodies against IROMPs and CP. Animals inoculated with the combination vaccine showed increased levels of antibodies against IROMPs, Lkt and CP. There was significant correlation between lung and serum antibodies against Lkt, CP and IROMPs. Animals that received the combination vaccine had significantly lower mean Pneumonic lung score as compared to SSE and control groups. The animals which received CS vaccine had mean Pneumonic lung score significantly lower than that of control group. A strong negative correlation existed between serum antibody levels against Lkt, IROMPs, CP and Pneumonic lung scores. The results from this study demonstrate the usefulness of CS vaccine alone or in combination with SSE vaccine in bringing about optimal protection in vaccinated calves, against experimental Pneumonic Pasteurellosis.

  • increased tumor necrosis factor α and interleukin 1β expression in the lungs of calves with experimental Pneumonic Pasteurellosis
    Veterinary Immunology and Immunopathology, 1995
    Co-Authors: Han Sang Yoo, S K Maheswaran, Trevor R Ames, S Srinand, M Suresh
    Abstract:

    Abstract We used a well characterized Pneumonic Pasteurellosis model in calves to determine whether increased proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression and secretion were associated with Pneumonic lesions. Bronchoalveolar lavage fluids, lavage cells consisting of alveolar macrophages and neutrophils with degenerative changes, and lung tissues were analyzed for the presence of TNF-α and IL-1β approximately 48 h following endobronchial inoculation of logarithmic phase Pasteurella haemolytica 12296 organisms. Levels of TNF-α and IL-1β mRNA were significantly increased in lavage cells of P. haemolytica-infected animals but not in cells from phosphate buffered saline (PBS) inoculated controls based on in situ hybridization analysis. Significantly increased levels of TNF-α, and IL-1β mRNA were also expressed within the Pneumonic lesions from P. haemolytica-infected calves. In contrast, lung tissues from PBS-inoculated control calves had cytokine mRNAs expressed at extremely low levels. Increased levels of bioactive IL-1 and immunoreactive (not bioactive) TNF-α were found in lavage fluids from P. haemolytica-infected calves compared with lavage fluids from PBS-inoculated calves. These findings indicate that the proinflammatory cytokines TNF-α and IL-1, may be associated with pathogenesis of lung injury in bovine Pneumonic Pasteurellosis.

Samuel K. Maheswaran - One of the best experts on this subject based on the ideXlab platform.

  • role of mannheimia haemolytica leukotoxin in the pathogenesis of bovine Pneumonic Pasteurellosis
    Animal Health Research Reviews, 2002
    Co-Authors: Samithamby Jeyaseelan, Srinand Sreevatsan, Samuel K. Maheswaran
    Abstract:

    Bovine Pneumonic Pasteurellosis continues to be a major respiratory disease in feedlot cattle despite the recent advances in our understanding of the underlying complexities of causation. The etiological agent, Mannheimia haemolytica , possesses several virulence factors, including capsule, outer membrane proteins, adhesins, neuraminidase, endotoxin and exotoxic leukotoxin. Accumulating scientific evidence implicates leukotoxin as the primary factor contributing to clinical presentation and lung injury associated with this disease. Unlike other virulence factors, leukotoxin shows cell-type- and species-specific effects on bovine leukocytes. Recent investigations have delineated the mechanisms underlying the target-cell-specificity of leukotoxin and how this contributes to the pathogenesis of lung damage. This review summarizes current understanding of the secretion, regulation, mechanisms of action and evolutionary diversity of leukotoxin of M. haemolytica . Understanding the precise molecular mechanisms of leukotoxin is critical for the development of more effective prophylactic and therapeutic strategies to control this complex disease.

  • The Biphasic mRNA Expression Pattern of Bovine Interleukin-8 in Pasteurella haemolytica Lipopolysaccharide-Stimulated Alveolar Macrophages Is Primarily due to Tumor Necrosis Factor Alpha
    Infection and immunity, 1998
    Co-Authors: Rhonda L. Lafleur, Mitchell S Abrahamsen, Samuel K. Maheswaran
    Abstract:

    Pasteurella haemolytica serotype 1 is the bacterial agent responsible for the pathophysiological events associated with bovine Pneumonic Pasteurellosis. Our previous studies support a role for the lipopolysaccharide (LPS) from P. haemolytica in the induction of proinflammatory cytokines. One of the pathological hallmarks of bovine Pneumonic Pasteurellosis is an influx of neutrophils into the alveolar spaces. This pronounced influx suggests the local production of a chemotactic factor(s) such as interleukin-8 (IL-8). In the context of the lung, the alveolar macrophage appears to be the major producer of IL-8, a proinflammatory cytokine with potent neutrophil chemotactic activity. By using Northern blot analysis, we have examined the kinetics of IL-8 mRNA expression in P. haemolytica LPS-stimulated bovine alveolar macrophages and found that 1 ng of LPS per ml induces maximal expression of IL-8 mRNA. The results also indicate a biphasic time course expression pattern in which IL-8 mRNA levels peak between 1 and 2 h in the first phase and between 16 and 24 h in the second phase (P < 0.01). In addition, monospecific polyclonal antibodies were used to demonstrate the role of tumor necrosis factor alpha (TNF-α) in the second phase of IL-8 mRNA expression. Our findings support a role for P. haemolytica LPS and TNF-α in the induction of IL-8 from bovine alveolar macrophages.

  • Leukotoxin As a Virulent Factor of Pasteurella Haemolytica
    1992
    Co-Authors: Samuel K. Maheswaran, Trevor R Ames, Han Sang Yoo, L O Whiteley, Evelyn L. Townsend, David Weiss, C. Gonzalez, Mathur S. Kannan
    Abstract:

    Pasteurella haemolytica biotype A, serotype 1 (Al) has been established as the primary agent responsible for the clinical disease and pathophysiologic events leading to acute lobar fibrinonecrotizing pneumonia associated with bovine Pneumonic Pasteurellosis(1,2,3). The bacteria produces several potential virulent factors, of which the leukotoxin (LKT) has received the most attention(4). The LKT is a heat-labile proteinaceous exotoxin, that is oxygen-stable, non-dialyzable, water soluble, and is produced in high concentrations by P.haemolytica during the logarithmic phase of growth(5). The genes that code for the synthesis and secretion of this LKT have been cloned(6). All 15 serotypes of P. haemolytica produce LKT(7). It has a molecular weight of 101-105kDa when determined by sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis(8). Attempts to purify the LKT has been futile because it is tightly bound to the LPS and there is no efficient way to remove the LPS without inactivating the LKT. It is one of a family of RTX(repeat toxins)-pore forming cytolysin which has a unique specificity, in that it is only cytocidal to ruminant leukocytes(9). This cytotoxicity is caused by the formation of pores in the cell membrane which allows the influx of calcium and results in a sequence of cell-damaging events(lO). Since this organism produces disease only in ruminants, this would support the role of LKT as a virulence factor. Indeed, several observations point to the central role that LKT has in the pathogenesis of Pneumonic Pasteurellosis. For example, in experimental Pasteurellosis, the clinical and pathophysiologic events are dose-dependently reproduced by the intatracheal administration of live logarithmic phase P. haemolytica and not by stationary phase organisms(ll). This enhanced pathogenicity may be related to the amount of LKT produced by these different populations. Indeed, we (5) and others(12)* have shown that the logarithmic phase cells produce far greater amounts of this LKT than stationary cells. In other studies, cattle with high LKT neutralizing antibody titers have higher survival rates in the natural disease and experimental Pasteurellosis than animals with low antibody titers(13). Although advances have been made in describing the cytolytic properties of the P.haemolytica LKT, the mechanisms by which it brings about lung injury in cattle are poorly understood. Our laboratory has long been interested in elucidating the contributions and mechanisms by which the LKT induce this acute lung injury in Pneumonic Pasteurellosis. Three experiments were designed to study if the LKT contributed in the genesis of lung injury in Pneumonic Pasteurellosis.