| Abstract
|
:
|
Maternal colostral and milk immunity plays a major role in protection of highly vulnerable mammalian neonates against microbial pathogens. The colostral and lactogenic defenses are comprised of specific (immunoglobulin-associated) immunity and nonspecific, innate (non-immunoglobulin) immunity. The research presented in this thesis was focused on humoral innate immune substances in porcine milk that bind to bacteria, prevent their attachment or inhibit their growth. Several porcine milk proteins were demonstrated to bid to lipopolysaccharide (LPS) of Escherichia coli (i.e. lactoferrin, α S1-casein, κ-casein, β-casein, serum amyloid A and CD14) or to F4ac fimbriae of E. coli (i.e. lactadherin, lipoprotein lipase, whey acidic protein, β-casein, actin, ezrin and moesin). After in vitro pepsin-digestion of porcine milk, lactoferrin, α S1-casein and κ-casein retained their binding capacity to LPS, and lactadherin, αS1-casein and heart-fatty-acid proteins to F4 fimbriae. In addition, we showed that porcine lactadherin significantly inhibited E. coli F4ac attachment to the intestinal villi in vitro. This inhibition was based on carbohydrate dependent interaction between porcine lactadherin and F4 fimbriae. Contrary to the previous reports that were based on short synthetic porcine lactoferricin B peptides, it was demonstrated that pepsin-digested porcine lactoferrin has potent antimicrobial activity in vitro against many porcine bacterial pathogens. In addition, it was shown that porcine milk can generate cationic cleavage fragments that exhibit broad-spectrum antimicrobial activity similar to the previously reported casocidin-I. Both of these anti-microbial substances inhibited growth of several porcine bacterial pathogens. Additional studies are needed to characterize further these purified antimicrobial substances in porcine milk and to fully assess their antimicrobial potency. Based on in vitro findings, it is reasonable to hypothesize that some of the above-listed substances may be involved in defense against pathogens in vivo. The future studies will need to determine if these substances are involved in host defense in vivo within a very complex gastrointestinal environment.
|