| Mannheimia haemolytica and its leukotoxin cause neutrophil extracellular trap formation by bovine neutrophils. | |
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MedLine Citation:
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PMID: 20823211 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mannheimia haemolytica is an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of M. haemolytica causes NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an ΔlktC mutant of M. haemolytica, we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT or M. haemolytica cells. Further investigation revealed that NETs formed in response to M. haemolytica are capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing of M. haemolytica cells in bovine NETs. Understanding NET formation in response to M. haemolytica and its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease. |
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Authors:
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Nicole A Aulik; Katrina M Hellenbrand; Heather Klos; Charles J Czuprynski |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-09-07 |
Journal Detail:
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Title: Infection and immunity Volume: 78 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-19 Completed Date: 2010-11-12 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 4454-66 Citation Subset: IM |
Affiliation:
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Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, WI 53706, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD18 / genetics, metabolism Cattle Cattle Diseases / microbiology, pathology Cell Line DNA / genetics, isolation & purification, metabolism* Exotoxins / immunology*, metabolism Extracellular Space / genetics, metabolism*, microbiology Histones / genetics, metabolism Leukocyte Count Leukocyte Elastase Lung / microbiology, pathology Mannheimia haemolytica / immunology, pathogenicity* Neutrophils / enzymology, immunology, metabolism* Pasteurellosis, Pneumonic / microbiology, pathology Proteins / metabolism Transfection |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD18; 0/Exotoxins; 0/Histones; 0/Proteins; 0/leukotoxin; 9007-49-2/DNA; EC 3.4.21.37/Leukocyte Elastase |
| Comments/Corrections | |
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