title: Effect of a biological response modifier on cellular death mechanisms at drying off.
abstract: Agents that increase natural protective mechanisms have been proposed for prevention and treatment of intramammary infections. The objective of this study was to describe the effects of a single intramammary infusion of a lipopolysaccharide (LPS)-based biological response modifier (BRM) on cellular death mechanism in uninfected and Staphylococcus aureus-infected bovine mammary glands during involution. Three groups of 12 cows, each one including 6 Staph. aureus-infected and 6 uninfected, were infused in two mammary quarters with BRM or placebo and slaughtered at 7, 14 and 21 d of involution. In infected quarters, BRM treatment produced a significant increase in percent of stained epithelial cells for the apoptosis-promoting protein Bax at every observation period. In addition, BRM produced a significant increase of immunostained stromal cells for Bax compared with placebo-treated quarters. BRM treatment produced an increase in percentages of epithelial cells staining with active caspase-3 at 7 d and 14 d of involution compared with placebo-treated quarters and a significant decrease in percentages of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive epithelial cells at 7 d and 21 d of involution. In addition, BRM treatment caused an increase in percentage of stromal cells immunostaining for active caspase-3 and TUNEL. An increase of active caspase-3 and TUNEL epithelial and stromal cell immunostaining was observed in Staph. aureus-infected compared with uninfected quarters. Cellular proliferation, determined by Ki-67 immunostaining, was increased in epithelial and stromal cells from Staph. aureus-infected compared with uninfected quarters at every observation period. These results provide new insights into the mechanism of mammary cell death in uninfected and Staph. aureus-infected bovine mammary gland during involution and illustrate the effects of LPS-based BRM on apoptosis and cell proliferation during mammary involution.
authors.affiliation: Facultad de Ciencias Veterinarias, Universidad Nacional del Litoral, Rvdo Padre Kreder 2805, 3080 Esperanza, Santa Fe, Argentina.
authors.forename: Bibliana E
authors.initials: BE
authors.lastname: Dallard
authors.forename: Celina
authors.initials: C
authors.lastname: Baravalle
authors.forename: Hugo
authors.initials: H
authors.lastname: Ortega
authors.forename: Valeria
authors.initials: V
authors.lastname: Ruffino
authors.forename: Silvia
authors.initials: S
authors.lastname: Heffel
authors.forename: Luis F
authors.initials: LF
authors.lastname: Calvinho
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007774:Lactation / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects; D008414:Mastitis, Bovine / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013203:Staphylococcal Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary; D013211:Staphylococcus aureus; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D008070:Lipopolysaccharides; D051028:bcl-2-Associated X Protein; D053148:Caspase 3