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Bovine respiratory disease (BRD) is a serious lower respiratory tract infection characterized by inflammation, intense neutrophil infiltration, fibrin disposition, and consolidation of the lungs. BRD, also known as shipping fever, is the primary cause of morbidity in the U.S. beef and dairy industries. It is estimated that North American loses between 600 million and 3 billion dollars per year leading to a major concern for producers. BRD is caused by various viral and bacterial pathogens including Mannheimia haemolytica and Histophilus somni. M. haemolytica, a normal nasal inhabitant, is an important bacterial agent that causes BRD. The most important virulence factor of M. haemolytica is its leukotoxin (LKT), which causes necrosis at high concentrations and apoptosis and extracellular trap (ET) formation at low concentrations. H. somni is not only another causative agent of BRD, which also causes reproductive, cardiac and neuronal diseases in cattle. It is believed that viral infection predisposes cattle to a secondary bacterial infection. Bovine herpes virus type 1 (BHV-1) is associated with BRD in cattle and has been demonstrated to synergize with M. haemolytica. Previous research has demonstrated that media removed from BHV-infected bovine bronchiolar epithelial (BBE) cells contained several cytokines including interferons, IL-1, TNF-α and IL-6. Pre-incubation of bovine neutrophils (bPMNs) with conditioned media from BHV-1 infected BBE cells increased bPMN migration, shape change, the expression of LFA-1, and the production of reactive oxygen species and degranulation. Previous research has shown that neutrophils and macrophages produce ETs in response to M. haemolytica and its LKT and H. somni. ETs are extracellular fibers of DNA and associated antimicrobial proteins that have been released by various leukocytes to trap and kill the pathogen. ET formation is distinct from apoptosis and necrosis. Here, we examine the role conditioned media, removed from BBE cells infected with BHV, plays in ET formation by bovine PMNs and macrophages in response to M. haemolytica or H. somni.

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Nicole Aulik



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