Delayed neutrophil apoptosis in bovine subclinical mastitis: Possible involvement in persistent accumulation of cells in milk

P. Boutet; L. Gillet; R. Closset; A. Vanderplasschen; F. Bureau; P. Lekeux

Delayed neutrophil apoptosis in bovine subclinical mastitis: Possible involvement in persistent accumulation of cells in milk

in Mastitis in dairy production

Autor:innen:

P. Boutet

P. Boutet ¹Department of Physiology, University of Liège, Liège, Belgium

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L. Gillet

L. Gillet ²Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium

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R. Closset

R. Closset ¹Department of Physiology, University of Liège, Liège, Belgium

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A. Vanderplasschen

A. Vanderplasschen ²Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium

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F. Bureau

F. Bureau ¹Department of Physiology, University of Liège, Liège, Belgium

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P. Lekeux

P. Lekeux ¹Department of Physiology, University of Liège, Liège, Belgium

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Art:: Kapitel

Seiten:: 208–214

DOI:: https://doi.org/10.3920/9789086865505_028

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Bovine subclinical mastitis can be defined as a moderated inflammatory disease characterized by a persistent accumulation of neutrophils in milk. As granulocytemacrophage colony-stimulating factor (GM-CSF)-mediated delay of neutrophil apoptosis contributes to the accumulation of inflammatory cells at the inflammation site in many human diseases, we sought to determine whether subclinical mastitis in cows is also associated with a GM-CSF-dependent increase in milk neutrophil survival. We first addressed the hypothesis that GM-CSF delays bovine neutrophil apoptosis by activation of members of the signal transducer and activator of transcription (STAT) family, which are critical regulators of the expression of various Bcl-2 family proteins. GM-CSF significantly delayed apoptosis of blood neutrophils obtained from healthy cows. In these cells, GM-CSF activated STAT5 and induced an increase in the mRNA of the anti-apoptotic Bcl-2 member, Bcl-x_L. This pathway was blocked by the Jak inhibitor, AG-490. This inhibition was associated with abrogation of the prosurvival effect of GM-CSF, demonstrating a key role for STAT5 in delayed neutrophil apoptosis. We further found that GM-CSF expression was increased in milk cells from subclinical mastitis-affected cows. Neutrophils from these cows demonstrated a significant delay of apoptosis as compared with neutrophils obtained from healthy cows. Active STAT5 complexes were detected in these neutrophils. Finally, in the presence of AG- 490, apoptosis in milk neutrophils from mastitis-affected cows was induced. These results indicate that neutrophil survival is enhanced in milk of subclinical mastitis-affected cows and suggest a role for a GM-CSF-activated STAT5 signaling pathway in this phenomenon. This pathway could thus represent a target for the control of persistent accumulation of neutrophils in the bovine mammary gland.

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Mastitis in dairy production

Current knowledge and future solutions

ISBN:: 9789086865505

Verleger:: Wageningen Academic

Print-Publikationsdatum:: 24 Oct 2005

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Delayed neutrophil apoptosis in bovine subclinical mastitis: Possible involvement in persistent accumulation of cells in milk

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Mastitis in dairy production

Current knowledge and future solutions

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