title: The effect of carbohydrate moiety structure on the immunoregulatory activity of lactoferrin in vitro.
abstract: The aim of this study was to evaluate the immunoregulatory effects of recombinant human lactoferrin (rhLF) in two in vitro models: (1) the secondary humoral immune response to sheep erythrocytes (SRBC); and (2) the mixed lymphocyte reaction (MLR). We compared the non-sialylated glycoform of rhLF as expressed by glycoengineered Pichia pastoris with one that was further chemically sialylated. In an earlier study, we showed that sialylated rhLF could reverse methotrexate-induced suppression of the secondary immune response of mouse splenocytes to SRBC, and that the phenomenon is dependent on the interaction of lactoferrin (LF) with sialoadhesin (CD169). We found that the immunorestorative activity of sialylated rhLF is also dependent on its interaction with the CD22 antigen, a member of the immunoglobulin superfamily that is expressed by B lymphocytes. We also demonstrated that only sialylated rhLF was able to inhibit the MLR reaction. MLR was inhibited by bovine lactoferrin (bLF), a glycoform that has a more complex glycan structure. Desialylated bLF and lactoferricin, a bLF-derived peptide devoid of carbohydrates, did not express such inhibitory activity. We showed that the interaction of LF with sialic acid receptors is essential for at least some of the immunoregulatory activity of this glycoprotein.
authors.affiliation: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Weigla 12, 53-114, Wrocław, Poland, zimecki@iitd.pan.wroc.pl.
authors.forename: Michał
authors.initials: M
authors.lastname: Zimecki
authors.forename: Jolanta
authors.initials: J
authors.lastname: Artym
authors.forename: Maja
authors.initials: M
authors.lastname: Kocięba
authors.forename: Maria
authors.initials: M
authors.lastname: Duk
authors.forename: Marian L
authors.initials: ML
authors.lastname: Kruzel
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002241:Carbohydrates / Q000737:chemistry*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010843:Pichia / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D012756:Sheep; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism
chemical_list: D002241:Carbohydrates; D011994:Recombinant Proteins; D063267:Sialic Acid Binding Ig-like Lectin 1; C082171:lactoferricin B; D007781:Lactoferrin; D008727:Methotrexate