Prion protein in milk.

BACKGROUND: Prions are known to cause transmissible spongiform encephalopathies (TSE) after accumulation in the central nervous system. There is increasing evidence that prions are also present in body fluids and that prion infection by blood transmission is possible. The low concentration of the proteinaceous agent in body fluids and its long incubation time complicate epidemiologic analysis and estimation of spreading and thus the risk of human infection. This situation is particularly unsatisfactory for food and pharmaceutical industries, given the lack of sensitive tools for monitoring the infectious agent. METHODOLOGY/PRINCIPAL FINDINGS: We have developed an adsorption matrix, Alicon PrioTrap, which binds with high affinity and specificity to prion proteins. Thus we were able to identify prion protein (PrP(C))--the precursor of prions (PrP(Sc))--in milk from humans, cows, sheep, and goats. The absolute amount of PrP(C) differs between the species (from microg/l range in sheep to ng/l range in human milk). PrP(C) is also found in homogenised and pasteurised off-the-shelf milk, and even ultrahigh temperature treatment only partially diminishes endogenous PrP(C) concentration. CONCLUSIONS/SIGNIFICANCE: In view of a recent study showing evidence of prion replication occurring in the mammary gland of scrapie infected sheep suffering from mastitis, the appearance of PrP(C) in milk implies the possibility that milk of TSE-infected animals serves as source for PrP(Sc).

Constitutive and regulated expression of platelet basic protein in human monocytes.

Platelet basic protein (PBP) and several of its derivatives are known for their broad range of functions as signaling molecules and cationic antimicrobial peptides and were considered hitherto megakaryocyte- and platelet-specific. In search of glucocorticoid-regulated antimicrobial systems of monocytes, we found a 15-fold down-regulation of PBP mRNA by differential display. Regulation was confirmed in vivo even at low prednisone doses. Quantitative mRNA analyses confirmed down-regulation also for platelets. Western blotting and immunostains showed down-regulation at the protein level. Pro-PBP derivatives were in the size range of 7.5-14 kD and in immunostains, gave granular cytoplasmatic patterns. Interleukin (IL)-4 and IL-10 induced a similar down-regulation. Phagocytosis resulted in an increase of smaller derivatives in the range of 7.5 kD. Stimulation with interferon-gamma and lipopolysaccharide did decrease expression of PBP and affected derivatization. Expression of PBP and its derivatives is not restricted to the megakaryocytic cell lineage. PBP and some of its derivatives might contribute to the antimicrobial armamentarium of mononuclear phagocytes or have monokine functions. Our studies define PBPs as one among the many immunosuppressive targets of glucocorticoids.