The host defense proteome of human and bovine milk

Kasper Hettinga, Hein van Valenberg, Sacco de Vries, Sjef Boeren, Toon van Hooijdonk, Johan van Arendonk, Jacques Vervoort, Kasper Hettinga, Hein van Valenberg, Sacco de Vries, Sjef Boeren, Toon van Hooijdonk, Johan van Arendonk, Jacques Vervoort

Abstract

Milk is the single source of nutrients for the newborn mammal. The composition of milk of different mammals has been adapted during evolution of the species to fulfill the needs of the offspring. Milk not only provides nutrients, but it also serves as a medium for transfer of host defense components to the offspring. The host defense proteins in the milk of different mammalian species are expected to reveal signatures of evolution. The aim of this study is therefore to study the difference in the host defense proteome of human and bovine milk. We analyzed human and bovine milk using a shot-gun proteomics approach focusing on host defense-related proteins. In total, 268 proteins in human milk and 269 proteins in bovine milk were identified. Of these, 44 from human milk and 51 from bovine milk are related to the host defense system. Of these proteins, 33 were found in both species but with significantly different quantities. High concentrations of proteins involved in the mucosal immune system, immunoglobulin A, CD14, lactoferrin, and lysozyme, were present in human milk. The human newborn is known to be deficient for at least two of these proteins (immunoglobulin A and CD14). On the other hand, antimicrobial proteins (5 cathelicidins and lactoperoxidase) were abundant in bovine milk. The high concentration of lactoperoxidase is probably linked to the high amount of thiocyanate in the plant-based diet of cows. This first detailed analysis of host defense proteins in human and bovine milk is an important step in understanding the function of milk in the development of the immune system of these two mammals.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflict to declare: TvH is an employee of FrieslandCampina, a dairy company that develops and markets dairy products. This did not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Overview of the amino acid…
Figure 1. Overview of the amino acid sequence of the 5 bovine cathelicidins found.
The red-colored amino acids designates the signaling peptide, the green-colored amino acids the cathelin-like domain and the black-colored amino acids the antimicrobial peptide. Bold amino acids are identical in >50% of the sequences, normal capitals show amino acids occurring in multiple sequences ad lower case amino acids occur in only one sequence. The peptides which were identified are underlined, and the yellow marking shows the peptides used for quantification. For comparison, also the amino acid sequence of the human cathelicidin is shown.
Figure 2. Overview of the experimental procedure.
Figure 2. Overview of the experimental procedure.

References

    1. German JB, Dillard CJ, Ward RE. Bioactive components in milk. Curr Opin Clin Nutr Metab Care. 2002;5:653–658.
    1. Severin S, Wenshui X. Milk biologically active components as nutraceuticals: review. Crit Rev Food Sci Nutr. 2005;45:645–656.
    1. Newburg DS. Bioactive components of human milk: evolution, efficiency, and protection. Adv Exp Med Biol. 2001;501:3–10.
    1. D'Allesandro A, Scaloni A, Zolla L. Human milk proteins: and interactomics and updated functional overview. J proteome Res. 2010;9:3339–3373.
    1. Smolenski G, Haines S, Kwan FY, Bond J, Farr V, et al. Characterisation of host defence proteins in milk using a proteomic approach. J Proteome Res. 2007;6:207–215.
    1. Affolter M, Grass L, Vanrobaeys F, Casado B, Kussmann M. Qualitative and quantitative profiling of the bovine milk fat globule membrane proteome. J Proteomics. 2010;73:1079–1088.
    1. Heid HW, Keenan TW. Intracellular origin and secretion of milk fat globules. Eur J Cell Biol. 2005;84:245–258.
    1. Charlwood J, Hanrahan S, Tyldesley R, Langridge J, Dwek M, et al. Use of Proteomic Methodology for the Characterization of Human Milk Fat Globular Membrane Proteins. Anal Biochem. 2002;301:314–324.
    1. Fortunato D, Giuffrida MG, Cavaletto M, Garoffo LP, Dellavalle G, et al. Structural proteome of human colostral fat globule membrane proteins. Proteomics. 2003;3:897–905.
    1. Reinhardt TA, Lippolis JD. Bovine milk fat globule membrane proteome. J Dairy Res. 2006;73:406–416.
    1. D'Amato A, Bachi A, Fasoli E, Boschetti E, Peltre G, et al. In-depth exploration of cow's whey proteome via combinatorial peptide ligand libraries. J Proteome Res. 2009;8:3925–3936.
    1. Reinhardt TA, Lippolis JD. Developmental changes in the milk fat globule membrane proteome during the transition from colostrum to milk. J Dairy Sci. 2008;91:2307–2318.
    1. Korhonen H, Marnila P, Gill HS. Milk immunoglobulins and complement factors. Br J Nutr. 2000;84:S75–S80.
    1. Porter P. Immunoglobulins in Bovine Mammary Secretions - Quantiative changes in early lactation and absorption by the neonatal calf. Immunology. 1972;23:225–238.
    1. Shah NP. Effects of milk-derived bioactives: an overview. Br J Nutr. 2000;84:S3–S10.
    1. Walker A. Breast milk as the gold standard for protective nutrients. J Pediatr. 2010;156:S3–S7.
    1. Allen WD, Porter P. Localization of immunoglobulins in intestinal mucosa and the production of secretory antibodies in response to intraluminal administration of bacterial antigens in the preruminant calf. Clin Exp Immunol. 1975;21:407–418.
    1. Kaetzel CS. The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunol Rev. 2005;206:83–99.
    1. Labeta MO, Vidal K, Mors JE. Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14. J Exp Med. 2002;191:1807–1812.
    1. Kovar MG, Serdula MK, Marks JS, Fraser DW. Review of the epidemiological evidence for an association between infant feeding and infant health. Pediatric. 1984;74:615–638.
    1. Sanderson IR, Walker WA. Chapter 14. Blackwell Science. Oxford, UK: 1999. Development of the gastrointestinal tract.
    1. Fox PF, McSweeney PLH. Kluwer academic plenum publishers. New York, NY, USA: 2003. Advanced dairy chemistry. Volume 1: proteins, 3rd edition. Chapter 12.4.
    1. Cho JK, Azuma N, Lee CH, Yu JH, Kanno C. Purification of membrane-bound lactoferrin from the human milk fat globule membrane. Biosci Biotechnol Biochem. 2000;64:633–635.
    1. Walstra P, Wouters JTM, Geurts TJ. CRC Press. Boca Raton, FL, USA: 2005. Dairy Science and Technology. 2nd edition. Chapters 2.7 and 16.6.
    1. Bu HF, Zuo XL, Wang X, Ensslin MA, Koti V, et al. Milk fat globule–EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. J Clin Invest. 2007;117:3673–3683.
    1. Hanayama R, Tanaka M, Miwa K, Shinohara A, Iwamatsu A, et al. Identification of a factor that links apoptotic cells to phagocytes. Nature. 2002;417:182–187.
    1. Nakatani H, Aoki N, Nakagawa Y, Jin-No S, Aoyama K, et al. Weaning-induced expression of a milk-fat globule protein, MFG-E8, in mouse mammary glands, as demonstrated by the analyses of its mRNA, protein and phosphatidylserine-binding activity. Biochem J. 2006;395:21–30.
    1. Dowbenko D, Kikuta A, Fennie C, Gillett N, Lasky LA. Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) mucin is expressed by lactating mammary gland epithelial cells and is present in milk. J Clin Invest. 1993;92:952–960.
    1. Hou Z, Bailey JP, Vomachka AJ, Matsuda M, Lockefeer JA, et al. Glycosylation-Dependent Cell Adhesion Molecule 1 (GlyCAM 1) Is Induced by Prolactin and Suppressed by Progesterone in Mammary Epithelium. Endocrinol. 2000;141:4278–4283.
    1. Armogida SA, Yannaras NM, Melton AL, Srivastava MD. Identification and quantification of innate immune system mediators in human breast milk. Allergy Asthma Proc. 2004;25:297–304.
    1. Murakami M, Dorschner RA, Stern LJ, Lin KH, Gallo RL. Expression and secretion of cathelicidin antimicrobial peptides in murine mammary glands and human milk. Pediatr Res. 2005;57:10–15.
    1. Oppenheim JJ, Yang D. Alarmins: chemotactic activators of immune responses. Curr Opin Immunol. 2005;17:359–365.
    1. Zanetti M, Gennaro R, Romeo D. Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett. 1995;374:1–5.
    1. Gillenwaters EN, Seabury CM, Elliott JS, Womack JE. Sequence analysis and polymorphism discovery in 4 members of the bovine cathelicidin gene family. J Hered. 2009;100:241–245.
    1. Mookherjee N, Wilson HL, Doria S, Popowych Y, Falsafi R, et al. Bovine and human cathelicidin cationic host defense peptides similarly suppress transcriptional responses to bacterial lipopolysaccharide. J Leukoc Biol. 2006;80:1563–1574.
    1. Lemay DG, Lynn DJ, Martin WF, Neville MC, Casey TM, et al. The bovine lactation genome: insights into the evolution of mammalian milk. Genome Biol. 2009;10:R43.
    1. Kussendrager KD, van Hooijdonk ACM. Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications. Br J Nutr. 2000;84:S19–25.
    1. Fonteh FA, Grandison AS, Lewis MJ. Variations of lactoperoxidase activity and thiocyanate content in cows' and goats' milk throughout lactation. J Dairy Res. 2002;69:401–409.
    1. Russell MW, Bobek LA, Brock JH, Hajishengallis G, Tenovuo J. Mucosal Immunology. Third Edition. In: Mestecky J, Lamm ME, McGhee JR, Bienenstock J, Mayer L, Strober W, editors. Chapter 5: Innate humoral defense factors. London, UK: Academic Press; 2005.
    1. Wiśniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat Methods. 2009;6:359–362.
    1. Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26:1367–1372.
    1. Peng JM, Elias JE, Thoreen CC, Licklider LJ, Gygi SP. Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: The yeast proteome. J Proteome Res. 2003;2:43–50.
    1. Silva JC, Gorenstein MV, Li GZ, Vissers JPC, Geromanos SJ. Absolute quantification of proteins by LCMSE - A virtue of parallel MS acquisition. Mol Cell Proteomics. 2006;5:144–156.

Source: PubMed

3
Suscribir