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Nutritional Immunology

A Peptide Derived from Bovine ß-Casein Modulates Functional Properties of Bone Marrow-Derived Macrophages from Germfree and Human Flora-Associated Mice¹

Catherine Sandré^*, Aude Gleizes^*, Françoise Forestier^*,2, Roseline Gorges-Kergot^*, Stefan Chilmonczyk, Joëlle Léonil^**, Marie-Christiane Moreau and Colette Labarre^*

Département de Microbiologie et Immunologie, Université Paris XI, Faculté de Pharmacie, Châtenay-Malabry Cedex, France; Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas Cedex, France; Laboratoire de Recherches de Technologie Laitière, Rennes Cedex, France; and Unité d’Ecologie et de Physiologie du Système Digestif, Institut National de la Recherche Agronomique, Jouy-en-Josas, France ^{** *}

²To whom correspondence should be addressed. E-mail: francoise.forestier{at}cep.u-psud.fr

ABSTRACT

The purpose of this study was to evaluate the immunomodulatory activity of a peptide derived from bovine ß-casein (ß-CN), the ß-CN (193–209) peptide, on mouse macrophages that were obtained either from germfree (GF) or from human flora-associated (HF) mice. Macrophages were derived from bone marrow (BMDM) in the presence of recombinant macrophage colony-stimulating factor and exposed to the peptide or lipopolysaccharide (LPS). Membrane marker expression [F4/80, Mac-1, major histocompatibility complex (MHC) class II antigens] and phagocytic activity were assessed by flow cytometry. Production of tumor necrosis factor- and interleukin (IL)-6 was measured by bioassays and production of IL-1, IL-1ß and IL-12 by ELISA. The expression of cytokine mRNA was determined using semi-quantitative reverse transcription-polymerase chain reaction. The ß-CN (193–209) peptide up-regulated MHC class II antigen expression and phagocytic activity of BMDM from GF and HF mice. Its enhancing effect on phagocytosis was greater than that after LPS stimulation (P < 0.01). The peptide induced notable levels of cytokine mRNA in BMDM from GF and HF mice, but it was a significantly weaker inducer of cytokine secretion than LPS. Nevertheless, although flora implantation had no stimulatory influence on basal MHC class II and basal cytokine levels, cells from HF mice were more susceptible than those from GF mice to the peptide effects on these variables. These results indicate that the ß-CN (193–209) peptide could enhance antimicrobial activity of macrophages without proinflammatory effects.

KEY WORDS: • milk peptide • macrophage • membrane antigen • phagocytosis • cytokine • mice