Lipid kinase activity of antibodies from milk of clinically healthy human mothers

Gorbunov, Dmitrii V.; Karataeva, N. A.; Buneva, Valentina N.; Nevinsky, Georgy A.

doi:10.1016/j.bbalip.2005.06.007

Cited by 25 publications

(48 citation statements)

References 30 publications

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“…Polyclonal IgGs and sIgAs with different catalytic activities are usually very heterogeneous in their affinity for different specific substrates and can be separated into many subfractions by chromatography on specific affinity sorbents [4]–[6], [9], [14]–[16], [18]–[21]. We have obtained sIgAs from the milk of five women and first analyzed their affinity for DNA and ATP by chromatography on DNA-cellulose and ATP-Sepharose, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…2 demonstrates representative data for one (sIgA-1) of five individual sIgA preparations. In contrast to previous studies [6], [16], [18], [20], [21], we have analyzed relative catalytic activities (RAs) of the sIgA fractions eluted from DNA-cellulose not only in the hydrolysis of plasmid DNA, but also in the hydrolysis of ATP and oligosaccharides as well as in phosphorylation of proteins, lipids and oligosaccharides (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

“…Phosphorylation of lipids and oligosaccharides tightly bound to the sIgAs was analyzed as in [21]–[23]. The reaction mixtures (20 µl) contained 10 mM Tris-HCl (pH 7.5), 1 mM MgCl 2 , 0.1 mM EDTA, 70 mM NaCl, 0.1 µM [ 32 P] ortho phosphate (20 µCi), and 20–100 µg/ml sIgAs.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, convincing evidence was provided using different approaches including several strict criteria that DNase, RNase [14]–[16], amylase [17], ATPase [18], and protease [19] as well as protein kinase [20], lipid kinase [21], and polysaccharide kinase [22], [23] enzymatic activities are intrinsic to human milk IgGs and sIgAs. In contrast to canonical enzymes, milk IgG and sIgA abzymes possess a unique capability to phosphorylate milk proteins and tightly bound with these Abs minor lipids and oligosaccharides having unusual structure in the presence of [ 32 P] ortho phosphate [20]–[23].…”

Section: Introductionmentioning

confidence: 99%

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Human Milk sIgA Molecules Contain Various Combinations of Different Antigen-Binding Sites Resulting in a Multiple Binding Specificity of Antibodies and Enzymatic Activities of Abzymes

2012

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In the classic paradigm, immunoglobulins are monospecific molecules that have stable structures and two or more identical antigen-binding sites. However, we show here for the first time that the sIgA pool of human milk contains, depending on the donor, only 35±5% λ-sIgAs, 48±7% κ-sIgAs, and 17±4% of chimeric λ-κ-sIgAs. sIgA preparations contained no traces of canonical enzymes. However, all sIgA fractions eluted from several specific affinity sorbents under the conditions destroying even strong immune complexes demonstrated high catalytic activities in hydrolysis of ATP, DNA, and oligosaccharides, and phosphorylation of proteins, lipids, and oligosaccharides. Sequential re-chromatographies of the sIgA fractions with high affinity to one affinity sorbents on the second, third and then fourth affinity sorbents bearing other immobilized antigens led to the distribution of Abs and all catalytic activities all over the profiles of these chromatographies; in all cases some fractions eluted from affinity sorbents only under the conditions destroying strong immune complexes. In vitro, only an addition of reduced glutathione and milk plasma containing no Abs to two sIgA fractions with different affinity for DNA-cellulose led to a transition of up to 11–20% of Ab from one fraction to the other. Our data are indicative of the possibility of half-molecule exchange between different IgA and sIgA molecules. In addition, it cannot be excluded that during the penetration of IgAs through the specific milk barrier, the secretory component (S) and the join chain (J) can combine molecules of dimeric H2L2 λ-IgAs and κ-IgAs against different antigens forming many different variants of H4L4SJ sIgA molecules. Therefore, some chimeric molecules of sIgA can contain from two to four HL-fragments to various antigens interacting with high affinity with different sorbents and catalyzing various chemical reactions. Our data essentially expand the ideas concerning explanation of the phenomenon of polyspecificity and cross-reactivity of Abs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Milk sIgA Molecules Contain Various Combinations of Different Antigen-Binding Sites Resulting in a Multiple Binding Specificity of Antibodies and Enzymatic Activities of Abzymes

2012

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“…Besides, natural catalytic antibodies which belong to sIgA and IgG classes have been found in woman's colostrum and milk [2,4]. Those abzymes possessed a capacity to phosphorylate proteins [5,6], lipids [7,8], and polysaccharides [9]. They also cleaved plasmid DNA [10], tRNA [11], nucleotides [12], polysaccharides [13], and casein [14].…”

Section: Introductionmentioning

confidence: 99%

DNA-hydrolyzing activity of sIgA-abzymes of human milk is differentially inhibited by nucleoside triphosphates

Kit

2009

Biol. Stud.

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It is known that human milk contains secretory immunoglobulines A (sIgA-abzymes) possessing affinity to mammalian DNA and capacity to cleave plasmid DNA. Regulation of DNA-hydrolyzing activity of those sIgA-abzymes is poorly studied. Here we investigate the effect of nucleoside triphosphates towards the DNase activity of sIgA-abzymes which were purified from human milk by a sequential chromatography on protein A-agarose, DEAE-Fractogel, and DNA-cellulose. By using DNA-hydrolysing assay, we revealed that 1 mM ATP and 1 mM dATP markedly reduced the cleavage of linear form of plasmid DNA by sIgA-abzymes, while the effect of GTP, CTP, TTP and dGTP was much weaker. dCTP and dTTP did not influence DNase activity of the sIgA-abzymes. Possible mechanisms of nucleotide-mediated inhibition of the DNase activity of sIgA-abzymes are discussed.

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Metal dependent hydrolysis of β-casein by sIgA antibodies from human milk

et al. 2010

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We present the first evidence that electrophoretically and immunologically homogeneous sIgAs purified from milk of healthy human mothers by chromatography on Protein A-Sepharose and FPLC gel filtration contain intrinsically bound metal ions (Ca > Mg ≥ Al > Fe approximately Zn ≥ Ni ≥ Cu ≥ Mn), the removal of which by a dialysis against ethylenediamine tetraacetic acid (EDTA) leads to a significant decrease in the β-casein-hydrolyzing activity of these antibodies (Abs). An affinity chromatography of total sIgAs on benzamidine-Sepharose interacting with canonical serine proteases separates a small metalloprotease sIgA fraction (6.8 ± 2.4%) from the main part of these Abs with a serine protease-like β-casein-hydrolyzing activity. The relative activity of this metalloprotease sIgA fraction containing intrinsically bound metal ions increases ∼1.2-1.9-fold after addition of external metal ions (Mg(2+) > Fe(2+) > Cu(2+) ≥ Ca(2+) ≥ Mn(2+)) but decreases by 85 ± 7% after the removal of the intrinsically bound metals. The metalloprotease sIgA fraction free of intrinsic metal ions demonstrates a high β-casein-hydrolyzing activity in the presence of individual external metal ions (Fe(2+) > Ca(2+) > Co(2+) ≥ Ni(2+)) and especially several combinations of metals: Co(2+) + Ca(2+) < Mg(2+) + Ca(2+) < Ca(2+) + Zn(2+) < Fe(2+) + Zn(2+) < Fe(2+) + Co(2+) < Fe(2+) + Ca(2+). The patterns of hydrolysis of a 22-mer oligopeptide corresponding to one of sIgA-dependent specific cleavage sites in β-casein depend significantly on the metal used. Metal-dependent sIgAs demonstrate an extreme diversity in their affinity for casein-Sepharose and chelating Sepharose, and interact with Sepharoses bearing immobilized monoclonal mouse IgGs against λ- and κ-type light chains of human Abs. Possible ways of the production of metalloprotease abzymes (Abz) by human immune system are discussed.

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Lipid kinase activity of antibodies from milk of clinically healthy human mothers

Cited by 25 publications

References 30 publications

Human Milk sIgA Molecules Contain Various Combinations of Different Antigen-Binding Sites Resulting in a Multiple Binding Specificity of Antibodies and Enzymatic Activities of Abzymes

Human Milk sIgA Molecules Contain Various Combinations of Different Antigen-Binding Sites Resulting in a Multiple Binding Specificity of Antibodies and Enzymatic Activities of Abzymes

DNA-hydrolyzing activity of sIgA-abzymes of human milk is differentially inhibited by nucleoside triphosphates

Metal dependent hydrolysis of β-casein by sIgA antibodies from human milk

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