Veterinary Immunology and Immunopathology 143 (2011) 1–10 Contents lists available at ScienceDirect Veterinary Immunology and Immunopathology j ourna l ho me pag e: www.elsevier.com/locate/vetimm Review paper Calcium influx, a new potential therapeutic target in the control of neutrophil-dependent inflammatory diseases in bovines R.A. Burgos a,∗ , I. Conejeros a , M.A. Hidalgo a , D. Werling b , C. Hermosilla b a Laboratory of Molecular Pharmacology, Institute of Pharmacology and Morphophysiology, Faculty of Veterinary Science, Universidad Austral de Chile, Valdivia, Chile b Royal Veterinary College, Department of Pathology and Infectious Diseases, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, UK a r t i c l e i n f o Article history: Received 2 March 2011 Received in revised form 6 May 2011 Accepted 8 May 2011 Keywords: SOCE Neutrophils Calcium channel Inflammation Bovine a b s t r a c t Neutrophils are the first line of defense against pathogens in bovines; however, they are also one of the most aggressive cells during the inflammatory process, causing injury in surrounding tissues. At present, anti-inflammatory drugs are limited in acute diseases, such as pneumonia, mastitis and endometritis, because neutrophils are mostly insensitive. One of the earliest events during neutrophil activation is the increase in intracellular calcium concentration. The calcium movement is attributed to the release from intracel- lular stores and influx through the calcium channels in the plasma membrane, a process called store operated calcium entry (SOCE). Recently, several calcium influx blockers have been shown to have strong effects on bovine neutrophils, and this suggests that the manipulation of this pathway can be useful in the control of neutrophil functions during acute inflammatory processes. In this paper, we will review the role of calcium influx as a potential anti-inflammatory target and summarize the most recent evidences for this in bovine neutrophils. © 2011 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Calcium homeostasis: a role of Ca 2+ influx in neutrophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3. Ca 2+ influx inhibitors support the existence of SOCE in neutrophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 4. Role of Ca 2+ influx on the respiratory burst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 5. Role of Ca 2+ influx on neutrophils degranulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 6. Role of Ca 2+ influx on intracellular pH changes and effects of acidification on calcium fluxes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1. Introduction Neutrophils are the first line of defense to control infectious diseases, however can produce also collateral ∗ Corresponding author. Tel.: +56 63 293015; fax: +56 63 293187. E-mail address: rburgos1@uach.cl (R.A. Burgos). tissue damage (Nathan, 2006). In spite of the relevance of neutrophils in the inflammatory process, there is a need to reduce the secondary injuries under specific circum- stances. The machinery and molecules involved in the neutrophil responses are pre-packaged in cellular cyto- plasmic granules and are therefore immediately available 0165-2427/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.vetimm.2011.05.037