Soya protein hydrolysates modify the expression of various pro-inflammatory genes induced by fatty acids in ovine phagocytes.

The objective of the present study was to test the hypothesis that fatty acids are the circulating mediators acting in a pro-inflammatory manner towards activated circulating ovine monocyte/macrophages and neutrophils. Furthermore, whether soya protein hydrolysates (SPH) inhibit the fatty acid-induced increase in the production of pro-inflammatory responses by ovine phagocytes was tested in vitro. All the fatty acids tested (myristic, palmitic, palmitoleic, stearic and oleic) increased (P<0·01; C18>C16>C14) membrane-bound urokinase plasminogen activator (u-PA) and u-PA free binding sites in cell membranes of activated ovine blood monocytes/macrophages, but only the C18 fatty acids (stearic, oleic) were effective towards blood neutrophils. The C18 fatty acids up-regulated (P<0·05) the gene expression of u-PA, u-PA receptor, intercellular adhesion molecule 1 and inducible NO synthase (in monocytes) but not that of cyclo-oxygenase-2, integrin α X and plasminogen activator inhibitor types 1 and 2 by ovine phagocytes. SPH blocked completely or partially all C18 fatty acid-induced changes in the expression of various pro-inflammatory genes. In conclusion, fatty acids selectively 'activate' ovine phagocytes, suggesting that these cells 'sense' metabolic signals derived from adipocytes. Soya protein peptides inhibit all changes in gene expression induced by fatty acids in ovine phagocytes in vitro. This constitutes a novel mechanism of action.

Milk peptides and immune response in the neonate.

Bioactive peptides encrypted within the native milk proteins can be released by enzymatic proteolysis, food processing, or gastrointestinal digestion. These peptides possess a wide range of properties, including immunomodulatory properties. The first months of life represent a critical period for the maturation of the immune system because a tolerance for nutrient molecules should be developed while that for pathogen-derived antigens is avoided. Evidence has accumulated to suggest that milk peptides may regulate gastrointestinal immunity, guiding the local immune system until it develops its full functionality. Our data using the weaning piglet as the model suggest that several milk peptides can downregulate various immune properties at a time (one to two weeks after weaning) that coincides with immaturity of the immune system. The protein kinase A system and/or the exchange protein directly activated by cyclic AMP (Epac-1) are implicated in the mechanism through which milk peptides can affect immune function in the early postweaning period. Despite the fact that the research in this field is in its infancy, the evidence available suggests that milk protein peptides may promote development of neonatal immune competence. Milk contains a variety of components that provide immunological protection and facilitate the development of neonatal immune competence. Two main categories of milk compounds are thought to be associated with immunological activity. The first category includes cytokines, which neonates do not produce efficiently. Cytokines present in milk are thought to be protected against intestinal proteolysis and could alleviate immunological deficits, aiding immune system maturation (Kelleher & Lonnerdal, 2001; Bryan et al., 2006). The second category of milk compounds includes milk protein peptides. Milk peptides may affect mucosal immunity possibly by guiding local immunity until it develops its full functionality (Baldi et al., 2005). This chapter focuses on the effects of milk peptides on immune function and attempts to provide an overview of the knowledge available in this field.

Acute mastitis induces upregulation of expression of plasminogen activator-related genes by blood monocytes and neutrophils in dairy ewes.

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 receptor (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 mammary 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.