Neutrophil influx into tissues occurs in many diverse diseases and can be associated with both beneficial and injurious effects. We hypothesize that the stimulus for certain neutrophilic inflammatory responses can be reduced to a series of competing reactions for iron, with either a labile or reactive coordination site available, between host chelators and chelators not indigenous to that specific living system. The iron focuses the transport of host phagocytic cells through a metal catalyzed generation of oxidant sensitive mediators including cytokines and eicosanoids. Many of these products are chemotactic for neutrophils. We also postulate that the iron increases the activity of the phagocyte associated NADPH oxidoreductase in the neutrophil. The function of this enzyme is likely to be the generation of superoxide in the host's attempt to chemically reduce and dislodge the iron from its chelate complex. After the reoxidation of Fe2+ in an aerobic environment, Fe3+ will be coordinated by host lactoferrin released by the neutrophil. When complexed by this glycoprotein, the metal does not readily undergo oxidation/reduction and is safely transported to the macrophages of the reticuloendothelial system where it is stored in ferritin. Finally, we propose that the neutrophil will attempt to destroy the chelator not indigenous to the host by releasing granular contents other than lactoferrin. Inability to eliminate the chelator allows this sequence to repeat itself, which can lead to tissue injury. Such persistence of a metal chelate in the host may be associated with biomineralization, fibrosis, and cancer.
BACKGROUND: Knowledge about the digestibility of the proteins in new products designed for feeding preterm infants is limited. The purpose of this study was to observe in vitro the hydrolysis of the bovine and human whey proteins in such products. METHODS: Proteins in human milk, in human milk fortifiers (Presemp [Semper AB, Stockholm, Sweden] and Enfamil [Mead Johnson, Evansville, IN, U.S.A.] human milk fortifiers), in preterm formulas (Similac Special Care [Ross, Columbus, OH, U.S.A.] and Enfalac [Mead Johnson]), and whey protein concentrates with varying degrees of denaturation were digested by duodenal juice from healthy preterm infants, from a 3-year-old child, and from adults. Digestion was studied in vitro using polyacrylamide gradient gel electrophoresis, electroimmunoassay, and nonprotein nitrogen analysis. RESULTS: Casein was the protein most rapidly degraded in all products. Human and bovine whey proteins were more slowly digested; as much as 68% of human lactoferrin was still immunoreactive after 40 minutes of digestion. The corresponding figure for bovine serum albumin was 24-69%; for B-lactoglobulin, 20-40%; for bovine alpha-lactalbumin, 20-51%; and for human alpha-lactalbumin, 41%. Contrary to common belief, digestibility of bovine whey proteins decreased with a high degree of denaturation of the proteins. CONCLUSIONS: Bovine whey proteins in human milk fortifiers and in preterm formulas are relatively slowly digested in vitro by normal duodenal juice. The results may have implications for the design of products for feeding preterm infants.
The contents of total nitrogen, nonprotein nitrogen, lactose, and individual milk proteins have been determined in human milk from well-nourished Swedish mothers. Breast milk samples from 50 mothers at different stages of lactation (up to 170 days) were collected. Furthermore, three mothers gave samples repeatedly throughout the whole lactation period. The protein content in mature milk was found to be 0.8 to 0.9% by amino acid analysis. The nitrogen content and the contents of the major human milk whey proteins, alpha-lactalbumin and lactoferrin, are very high for the first few days, then decrease rapidly and reach, thereafter, the more slowly declining level of mature milk. Nonprotein nitrogen and the nonspecific milk protein serum albumin are present in constant concentrations throughout lactation. The daily milk volumes were determined and found to be 500 to 600 ml in the very early part and 700 to 800 ml in the later part of the lactation period.