Veterinary Immunology and Immunopathology 138 (2010) 124–128 Contents lists available at ScienceDirect Veterinary Immunology and Immunopathology journal homepage: www.elsevier.com/locate/vetimm Short communication Acute mastitis induces upregulation of expression of plasminogen activator-related genes by blood monocytes and neutrophils in dairy ewes Georgios Theodorou a,∗ , Marina Daskalopoulou a , Roubini Chronopoulou a , Antonella Baldi b,c , Vittorio Dell’Orto b , Ioannis Politis a a Department of Animal Science and Aquaculture, Agricultural University of Athens, 75 Iera Odos St., 11855 Athens, Greece b Department of Veterinary Science and Technologies for Food Safety, Università degli Studi di Milano, Via Celoria 10, Milan, Italy c Centro interdipartimentale di studi Ghiandola mammaria (CISMA), Università degli Studi di Milano, Via Celoria 10, Milano, Italy article info Article history: Received 8 April 2010 Received in revised form 17 June 2010 Accepted 2 July 2010 Keywords: Mastitis Blood phagocytes Urokinase plasminogen activator system abstract The main objective of the present study was to examine whether genes implicated in the plasminogen activating cascade: urokinase-type plasminogen activator (u-PA), u-PA recep- tor (u-PAR) and plasminogen activator inhibitors type 1 (PAI-1) and type 2 (PAI-2) are expressed in a differential manner in ovine blood monocytes and neutrophils obtained from healthy and mastitic dairy ewes. A total of 48 blood samples were collected from 8 healthy and 8 mastitic dairy ewes over a period of 3 weeks. Streptococcus agalactiae was detected in milk samples isolated from mastitic animals. Results indicated that expression of all four genes was very low in monocytes and neutrophils isolated from healthy animals. In contrast, there was a 2- to 5-fold increase (P < 0.05) in expression of all four genes in monocytes and an 18- to 38-fold increase (P < 0.01) in neutrophils isolated from mastitic animals. In conclusion, upregulation of expression of u-PA and u-PAR by monocytes and neutrophils is probably related to the rapidity of migration of these cells towards the mam- mary gland, while the upregulation of PAI-1 and PAI-2 is a rather enigmatic observation and it is probably related to the successful localization of the infection. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Despite improved hygiene and management proce- dures, which include teat dipping, nonlactating treatment and use of antibiotics, mastitis is the most common and costly contagious disease affecting dairy farms in the west- ern world (Bradley, 2002). Migration of neutrophils to the Abbreviations: PAI-1, plasminogen activator inhibitor type 1; PAI-2, plasminogen activator inhibitor type 2; SCC, somatic cell count; u-PA, urokinase plasminogen activator; u-PAR, urokinase plasminogen activa- tor receptor. ∗ Corresponding author. Tel.: +30 2105294450; fax: +30 2105294442. E-mail address: gtheod@aua.gr (G. Theodorou). site of infection is the typical manifestation of an inflam- matory response. In the bovine mammary gland during mastitis, neutrophils start their migration by penetrating blood capillaries and crossing the mammary epithelium. Neutrophils accumulate on the luminal surface of the epithelium and then adhere to epithelial cells before detaching into the milk (Craven and Williams, 1985). Extracellular proteolysis of basement membranes and matrix is required for neutrophil diapedesis and migration to inflammatory sites (Politis, 2000). Neutrophil elastase and matrix metalloproteinases are among the enzymes involved in these processes (Kolaczkowska et al., 2009). The role of genes involved in the plasminogen activating cascade, especially that of urokinase plasminogen activator receptor (u-PAR) as a regulator of the rapidity of migra- 0165-2427/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2010.07.002