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Potential of nanoparticles containing matrix metalloproteinase-9 (MMP-9) as a dry-off enhancer: Pulling apart the effects of MMP-9 and nanoparticles.

A. Bach

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06-22-2020

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Abstract:

M85
Potential of nanoparticles containing matrix metalloproteinase-9 (MMP-9) as a dry-off enhancer: Pulling apart the effects of MMP-9 and nanoparticles.
L. Gifre-Renom1, J. V. Carratal�2, S. Par�s1, L. Sanchez-Garcia2, N. Ferrer-Miralles2,3, A. Villaverde2,3, A. Bach*4,1, E. Garcia-Fruit�s1, A. Ar�s1. 1Department of Ruminant Production, Institut de Recerca i Tecnologia Agroaliment�ries (IRTA Caldes de Montbui, Catalonia, Spain, 2Institut de Biotecnologia i de Biomedicina, Universitat Aut�noma de Barcelona Cerdanyola del Vall�s, Catalonia, Spain, 3Departament de Gen�tica i de Microbiologia, Universitat Aut�noma de Barcelona Cerdanyola del Vall�s, Catalonia, Spain, 4Instituci� Catalana de Recerca i Estudis Avan�ats (ICREA) Barcelona, Catalonia, Spain.

The dry period is a non-milking interval when the mammary gland involutes and regenerates to guarantee an optimal milk production in the subsequent lactation. Several bottlenecks such as the high risk of intramammary infections may hamper this process. Antibiotics have been routinely used as a preventive treatment, but the concerns about potential antibiotic resistance calls for alternative preventive strategies. Matrix metalloproteinase 9 (MMP-9) is an enzyme able to degrade the extracellular matrix, triggering the involution and immune function of the mammary gland. Thus, the objective of this study was to determine in vivo whether the involution and immune function enhancement previously observed after the administration of inclusion bodies (IB) containing MMP-9 was due to the nanoparticle format or to the inherent properties of the MMP-9 comprised in IB. Eight cows were enrolled in this study and 30 quarters of these cows were considered the experimental unit (4 quarters per cow in 7 cows, and 2 quarters in 1 cow). A dose of 1.2 mg of both active and inactive MMP-9 IB and 10 mL of saline solution were infused into 10 quarters per treatment at dry-off. At 1, 3, 6, and 9 d after protein infusions, mammary gland secretions (MGS) were obtained and analyzed for SCC, immune cell populations, BSA, lactoferrin, Na+/K+, and endogenous MMP-9. Data were analyzed using a fixed-effects model. There were only minor differences in the parameters monitored between the infusion of active or inactive rMMP-9 IB. Briefly, concentration of BSA in MGS were greater at 1 and 6 d in quarters treated with active rMMP-9 IB (P < 0.01) than those treated with inactive IB. Similarly, the Na+/K+ ratio in MGS increased at d 6 and was sustained at d 9 (P < 0.01) with the active MMP-9 IB compared with the inactive IB. Thus, the minor differences triggered by the administration of an active or an inactive form of MMP-9 led to conclude that the response observed in the bovine mammary gland was mainly due to the protein format (nanoparticle or soluble) but not to the biological activity of the MMP-9 embedded in the IB. This study provides relevant information on the future use of protein IB in the mammary gland of cows and the role of MMP-9 at dry-off.

Keywords: dry period, inclusion body, mammary gland.