Respiratory infection of cattle with bovine herpesvirus type 1 (BHV-1) predisposes cattle to secondary pneumonia with Mannheimia haemolytica as part of the bovine respiratory disease complex (BRD). One cell type that has received limited investigation for its role in the inflammation that accompanies BRD is the respiratory epithelial cell. In the present study we investigated mechanisms by which BHV-1 infection of respiratory epithelial cells contributes to the recruitment and activation of bovine polymorphonuclear neutrophils (PMNs) in vitro. Primary cultures of bovine bronchial epithelial (BBE) cells were infected with BHV-1 and assessed for cytokine expression by real-time PCR. We found that BHV-1 infection elicits a rapid IL-1, IL-8 and TNF-alpha mRNA response by BBE cells. Bovine PMNs exhibited greater adherence to BHV-1 infected BBE cells than uninfected cells. The increased adherence was significantly reduced by the addition of an anti-IL-1beta antibody or human soluble TNF-alpha receptor (sTNF-alphaR). Pre-incubation of bovine PMNs with conditioned media from BHV-1 infected BBE cells increased PMN migration, which was inhibited by addition of an anti-IL-1beta antibody, sTNF-alphaR, or an IL-8 peptide inhibitor. Conditioned media from BHV-1 infected BBE cells activated bovine PMNs in vitro as demonstrated by PMN shape change, production of reactive oxygen species and degranulation. PMNs also exhibited increased LFA-1 expression and susceptibility to M. haemolytica LKT following incubation with BHV-1 infected BBE cell conditioned media. Our results suggest that BHV-1 infection of BBE cells triggers cytokine expression that contributes to the recruitment and activation of neutrophils, and amplifies the detrimental effects of M. haemolytica LKT.
"Pro-inflammatory cytokines induce integrin expression and redistribution of leukocytes, which contribute to their recruitment and activation at the site of inflammation [15,16], as well as increasing vascular permeability and tissue injury [17,18]. There is evidence that inflammatory cytokines are the main orchestrators of the inflammatory cascade in BRDC, detecting high levels of TNFα and IL-1 in the airways of cattle infected with respiratory pathogens [19-22]. "
[Show abstract][Hide abstract] ABSTRACT: Resistance to respiratory disease in cattle requires host defense mechanisms that protect against pathogens which have evolved sophisticated strategies to evade them, including an altered function of pulmonary macrophages (MPhis) or the induction of inflammatory responses that cause lung injury and sepsis. The aim of this study was to clarify the mechanisms responsible for vascular changes occurring in the lungs of calves infected with bovine viral diarrhea virus (BVDV) and challenged later with bovine herpesvirus type 1 (BHV-1), evaluating the role of MPhis in the development of pathological lesions in this organ. For this purpose, pulmonary lesions were compared between co-infected calves and healthy animals inoculated only with BHV-1 through immunohistochemical (MAC387, TNFalpha, IL-1alpha, iNOS, COX-2 and Factor-VIII) and ultrastructural studies. Both groups of calves presented important vascular alterations produced by fibrin microthrombi and platelet aggregations within the blood vessels. These findings were earlier and more severe in the co-infected group, indicating that the concomitance of BVDV and BHV-1 in the lungs disrupts the pulmonary homeostasis by facilitating the establishment of an inflammatory and procoagulant environment modulated by inflammatory mediators released by pulmonary MPhis. In this regard, the co-infected calves, in spite of presenting a greater number of IMPhis than single-infected group, show a significant decrease in iNOS expression coinciding with the presence of more coagulation lesions. Moreover, animals pre-inoculated with BVDV displayed an alteration in the response of pro-inflammatory cytokines (TNFalpha and IL-1), which play a key role in activating the immune response, as well as in the local cell-mediated response.
Veterinary Research 03/2013; 44(1):20. DOI:10.1186/1297-9716-44-20 · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The d-vector in possible spin triplet superconductor Na2CoO2 (.) gamma H2O is microscopically analyzed on the basis of the multi-orbital Hubbard model including the atomic spin-orbit coupling. As a result of the perturbation theory, it is shown that the d-vector is parallel to the plane when the pairing symmetry is p-wave, while both d parallel to xy and d parallel to z are possible in the f-wave state. We point out that the multiple phase transitions are expected tinder the in-plane magnetic field when the pairing symmetry is p-wave. (c) 2006 Elsevier B.V. All rights reserved.
Physica B Condensed Matter 05/2006; DOI:10.1016/j.physb.2006.01.321 · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bovine respiratory disease (BRD) involves complex interactions amongst viral and bacterial pathogens that can lead to intense pulmonary inflammation (fibrinous pleuropneumonia). Viral infection greatly increases the susceptibility of cattle to secondary infection of the lung with bacterial pathogens like Mannheimia haemolytica and Histophilus somni. The underlying reason for this viral/bacterial synergism, and the manner in which cattle respond to the virulence strategies of the bacterial pathogens, is incompletely understood. Bovine herpesvirus type 1 (BHV-1) infection of bronchial epithelial cells in vitro enhances the binding of M. haemolytica and triggers release of inflammatory mediators that attract and enhance binding of neutrophils. An exotoxin (leukotoxin) released from M. haemolytica further stimulates release of inflammatory mediators and causes leukocyte death. Cattle infected with H. somni frequently display vasculitis. Exposure of bovine endothelial cells to H. somnii or its lipooligosaccharide (LOS) increases endothelium permeability, and makes the surface of the endothelial cells pro-coagulant. These processes are amplified in the presence of platelets. The above findings demonstrate that bovine respiratory pathogens (BHV-1, M. haemolytica and H. somni) interact with leukocytes and other cells (epithelial and endothelial cells) leading to the inflammation that characterizes BRD.
Animal Health Research Reviews 12/2009; 10(2):141-3. DOI:10.1017/S1466252309990181
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