Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/16/2008
Publication Date: 12/15/2008
Citation: Rinaldi, M., Ceciliani, F., Lecchi, C., Moroni, P., Bannerman, D.D. 2008. Differential effects of alpha 1-acid glycoprotein on bovine neutrophil respiratory burst activity and IL-8 production. Veterinary Immunology and Immunopathology. 126:199-210. Interpretive Summary: Mastitis remains among the most costly and prevalent diseases in the dairy industry. This disease is often accompanied by inflammation-induced injury to mammary tissue, which can delay recovery and lead to prolonged reduction in milk output. The objective of the current study was to evaluate the immunomodulatory effects of an endogenously expressed acute phase protein, a1-acid glycoprotein (AGP), on neutrophil production of reactive oxygen species, the latter of which have been implicated in mastitis-associated tissue injury. The major finding of this study was that AGP inhibits the production of injurious reactive oxygen species without negatively impacting the ability of neutrophils to kill bacterial pathogens. The results of this study are important to the dairy industry and veterinarians as it establishes a beneficial role for AGP in protecting cows with mastitis against injury that is commonly associated with this disease. These findings form the basis for future studies investigating the therapeutic potential of AGP in preventing injury during mastitis and evaluating AGP as a biomarker of disease severity.
Technical Abstract: During bacterial-mediated diseases of dairy cows, such as mastitis, neutrophils (PMN’s) play a critical role in defending the host against invading pathogens. To carry out this role, PMN’s travel from the blood to the mammary gland in response to a variety of inflammatory mediators, including cytokines, complement, and leukotrienes. Interleukin (IL)-8, a pro-inflammatory cytokine produced by PMN’s, plays a fundamental role not only as chemoattractant but also stimulating PMN adherence, degranulation, and production of reactive oxygen species (ROS), the latter of which contributes to the bactericidal capabilities of these cells. ROS are produced intracellularly and can be released extracellularly. The aberrant extracellular release of ROS, however, has been reported to induce injury to host tissues during mastitis and other inflammatory-mediated diseases. The acute phase response (APR) occurs shortly after infection and/or tissue injury, and enhances the host response to infection while limiting the potential harmful effects of the inflammatory response on healthy tissues. One characteristic of the APR is the induction of a large number of plasma proteins referred to as acute phase proteins (APP). a1-acid glycoprotein (AGP) is an APP that increases in response to infection or injury in cattle and humans. The precise function of AGP is unknown, but it has been reported to possess anti-inflammatory properties. The objective of the current study was to evaluate the effects of bovine AGP on PMN pro-inflammatory responses including respiratory burst activity and cytokine production. Bovine AGP dose-dependently inhibited zymosan- induced PMN extracellular release of superoxide anion and hydrogen peroxide without affecting the capacity of PMN to engulf and kill Staphylococcus aureus. Moreover, AGP exerted its effect on ROS production regardless of whether PMN’s were exposed to AGP prior to or after activation. In contrast to respiratory burst activity, AGP enhanced PMN production of IL-8. The precise mechanism by which AGP regulates PMN functions remains unknown, but data presented in the current study suggest that AGP may have a complex role by differentially regulating PMN pro-inflammatory activities.