|Martinez, Alfredo - INSTITUTO CAJAL, MADRID|
|Cuttitta, Frank - NIH|
Submitted to: Domestic Animal Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 17, 2006
Publication Date: March 13, 2006
Citation: Elsasser, T.H., Capuco, A.V., Caperna, T.J., Martinez, A., Cuttitta, F., Kahl, S. 2006. Adrenomedullin (AM) and adrenomedullin binding protein (AM-BP) in the bovine mammary gland and milk: Effects of stage of lactation and experimental intramammary E. coli infection. Domestic Animal Endocrinology. Available:http://dx.doi.org/doi:10.1016/j.domaniend. 32:138-154. Interpretive Summary: Mastitis is the single most costly problem facing dairy producers and the antibiotic treatment of clinical cases as well as prophylactic treatment of dry cows with antibiotics to prevent mastitis in the following lactation increasingly is coming under scrutiny. Our present research was aimed at measuring tissue and milk levels of two proteins that are made by the cow herself and have excellent properties as natural defense against invading pathogens. Adrenomedullin and its binding protein are proteins naturally present in every vertebrate species that have multiple actions to regulate blood flow, immune function and general cellular health. Adrenomedullin is also a naturally occurring antimicrobial peptide, that is, it can kill bacteria that infect an organ. We measured these two proteins in bovine mammary tissue and milk at several stages of lactation as well as during an experimental infection with E. coli, a bacteria common to bovine mastitis. Our data indicated that adrenomedullin and its binding protein were present in milk and mammary tissue and the tissue levels of these changes during the lactation cycle. The greatest content of these proteins was detected in mammary tissues with high levels of somatic cells as well as mammary tissue infected with E. coli. The data suggest that AM may be a useful biomarker to select animals with greater capacity to fight mammary infection and decrease the levels of antibiotics used in some dairy management.
Technical Abstract: Adrenomedullin (AM) has been characterized as an endogenous tissue survival factor and modulator of many inflammatory processes. Because of the significant increase in susceptibility of the mammary gland to infection during the time surrounding parturition in the cow, we investigated how milk and tissue content of AM and its binding protein (AM-BP) might be affected by the stage of lactation and the udder health status. Milk and mammary biopsy samples were obtained from Holstein cows 21 d prior to and at various times after calving to represent the dry period and early and mid stages of lactation. Additional cows received an intramammary challenge with E. coli in one mammary quarter with biopsy samples subsequently collected (clean and infected quarters; 24 h) for immunohistochemical characterization of AM and AM-BP. Milk AM concentrations (radioimmunoassay) were relatively constant across the stages of lactation while AM-BP increased 2-fold (P<0.04) between early and mid-lactation. Milk AM (P<0.04) and AM-BP (P<0.03) increased as somatic cell counts (SSCs) increased within a given stage of lactation. Tissue content of both AM and AM-BP (quantitative immunohistochemistry) were significantly affected by stage of lactation, lowest in the dry period and progressively increasing to peak at mid lactation as well as increasing in association with higher levels of SSCs. Following E.coli challenge, tissue AM antigen increased in epithelial cells surrounding mammary lumen presenting high levels of SSCs with the highest immunostaining intensity present in the SSCs (neutrophils) themselves. The data suggest that AM and AM-BP are cooperatively regulated in the mammary gland during lactation; changes in localized tissue AM and AM-BP content reflect a dynamic regulation of these tissue factors in the bovine mammary gland consistent with their protective effects within inflamed tissue.