Potential of MMP-9 based nanoparticles at optimizing the cow dry period: pulling apart the effects of MMP-9 and nanoparticles

L Gifre-Renom,L Sánchez-García,N Ferrer-Miralles,Elena Garcia-Fruitós,A Villaverde,Anna Arís,S Parés,J V Carratalá,A Bach

doi:10.1038/s41598-020-67176-2

Abstract

The cow dry period is a non-milking interval where the mammary gland involutes and regenerates to guarantee an optimal milk production in the subsequent lactation. Important bottlenecks such as the high risk of intramammary infections complicate the process. Antibiotics have been routinely used as a preventive treatment but the concerns about potential antibiotic resistance open a new scenario in which alternative strategies have to be developed. Matrix metalloproteinase-9 (MMP-9) is an enzyme able to degrade the extracellular matrix, triggering the involution and immune function of cow mammary gland. We have studied the infusion into the mammary gland of MMP-9 inclusion bodies as protein-based nanoparticles, demonstrating that 1.2 mg of MMP-9 enhanced the involution and immune function of the cow mammary gland. However, the comparison of the effects triggered by the administration of an active and 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 but not to the biological activity of the MMP-9 embedded in the inclusion body. This study provides relevant information on the future use of protein inclusion bodies in cow mammary gland and the role of MMP-9 at dry-off.

Highlights

The cow dry period is a non-milking interval where the mammary gland involutes and regenerates to guarantee an optimal milk production in the subsequent lactation
We have determined in vivo, first, the lowest dose of recombinant MMP-9 (rMMP-9) inclusion body (IB) that boost innate immunity and mammary involution, and second, whether this was due to the nanoparticle format or to the inherent properties of the rMMP-9 comprised in these IBs11
Through the comparison of the effects triggered by the administration of an inactive form of rMMP-9 IB at dry-off with its active counterpart, the real potential of rMMP-9 IBs during the cow dry period has been distinguished

Summary

Introduction

The cow dry period is a non-milking interval where the mammary gland involutes and regenerates to guarantee an optimal milk production in the subsequent lactation. All used doses enhanced the recruitment of immune cells into mammary gland (namely SCC) up to 6 d post dry-off (Fig. 1a). This experiment replicated the results observed by Parés et al (2017)[8], consolidating the potential of rMMP-9 IBs www.nature.com/scientificreports to locally stimulate the recruitment of immune cells in the mammary gland at dry-off and to accelerate the onset of involution biomarkers after 24 h of infusions.

Results

Conclusion