Extracellular cyclophilin A possesses chemotaxic activity in cattle

International audienceCyclophilin A (CyPA) was originally discovered in bovine thymocytes as a cytosolic binding protein of the immunosuppressive drug cyclosporine A. Recent studies have revealed that in mice and humans, CyPA is secreted from cells in injured or infected tissues and plays a role in recruiting inflammatory cells in those tissues. Here we found that in cattle abundant level of extracellular CyPA was observed in tissues with inflammation. To aid in investigating the role of extracellular CyPA in cattle, we generated recombinant bovine CyPA (rbCyPA) and tested its biological activity as an inflammatory mediator. When bovine peripheral blood cells were treated with rbCyPA in vitro, we observed that rbCyPA reacts with the membranous surface of granulocytes, monocytes and lymphocytes. Chemotaxis analysis showed that the granulocytes migrate toward rbCyPA and the migration is inhibited by pre-treatment with an anti-bovine CyPA antibody. These results indicate that, as for mice and humans, extracellular CyPA possesses chemotactic activity to recruit inflammatory cells (e.g., granulocytes) in cattle, and could thus be a potential therapeutic target for the treatment of inflammation

Genetic aspects of immunoglobulins and cyclophilin A in milk as potential indicators of mastitis resistance in Holstein cows

ABSTRACT: Mastitis is one of the most frequent and costly diseases affecting dairy cattle. Natural antibodies (immunoglobulins) and cyclophilin A (CyPA), the most abundant member of the family of peptidyl prolyl cis/trans isomerases, in milk may serve as indicators of mastitis resistance in dairy cattle. However, genetic information for CyPA is not available, and knowledge on the genetic and nongenetic relationships between these immune-related traits and somatic cell score (SCS) and milk yield in dairy cattle is sparse. Therefore, we aimed to comprehensively evaluate whether immune-related traits consisting of 5 Ig classes (IgG, IgG1, IgG2, IgA, and IgM) and CyPA in the test-day milk of Holstein cows can be used as genetic indicators of mastitis resistance by evaluating the genetic and nongenetic relationships with SCS in milk. The nongenetic factors affecting immune-related traits and the effects of these traits on SCS were evaluated. Furthermore, the genetic parameters of immune-related traits according to health status and genetic relationships under different SCS environments were estimated. All immune-related traits were significantly associated with SCS and directly proportional. Additionally, evaluation using a classification tree revealed that IgA, IgG2, and IgG were associated with SCS levels. Genetic factor analyses indicated that heritability estimates were low for CyPA (0.08) but moderate for IgG (0.37), IgA (0.44), and IgM (0.44), with positive genetic correlations among Ig (0.25–0.96). We also evaluated the differences in milk yield and SCS of cows between the low and high groups according to their sires' estimated breeding value for immune-related traits. In the high group, IgA had a significantly lower SCS in milk at 7 to 30 d compared with that in the low group. Furthermore, the Ig in milk had high positive genetic correlations between healthy and infected conditions (0.82–0.99), suggesting that Ig in milk under healthy conditions could interact with those under infected conditions, owing to the genetic ability based on the level of Ig in milk. Thus, Ig in milk are potential indicators for the genetic selection of mastitis resistance. However, because only the relationship between immune-related traits and SCS was investigated in this study, further study on the relationship between clinical mastitis and Ig in milk is needed before Ig can be used as an indicator of mastitis resistance