DOI: https://doi.org/10.22141/2224-0551.12.3.2017.104219

The content of antimicrobial proteins in children with respiratory tract inflammatory diseases

G.A. Lezhenko, A.Ye. Abaturov, E.Ye. Pashkova, K.V. Gladun

Abstract


Background. Inflammatory diseases of the respiratory tract are often associated with impaired synthesis of antimicrobial peptides, whose representatives are defensins and lactoferrin (LF). The purpose of the study was to establish the concentrations of antimicrobial peptides in the oropharyngeal secretion and plasma in children with inflammatory diseases of the respiratory tract. Materials and methods. The study group included 111 children aged 4 to 17 years from orphanages. Сontent of antimicrobial proteins of LF, α-defensins 1–3 (human neutrophil peptides (HNP) 1–3), secretory immunoglobulin A in the oropharyngeal secretion, HNP 1–3 in the blood plasma, of interleukin 6 (IL-6) and -10 in the blood serum in children was measured by immunoassay. Results. Analysis of anamnestic data in somatically healthy children from orphanages showed the presence of 4 to 6 episodes of acute respiratory infections throughout the year, the duration of which averaged 5.3 ± 0.4 days. According to the results of the study, the content of α-defensins 1–3 in the blood plasma of the children of the control group was 3583.3 ± 735.4 pg/ml, while in the group of children with recurrent bronchitis, the HNP 1–3 level was almost twice higher — 6576.7 ± 602.8 pg/ml, p < 0.01. When studying the serum cytokine profile, it was found that in children with recurrent bronchitis compared with the control group, the content of proinflammatory IL-6, which regulates the inflammatory process and provides mobilization of the inflammatory response, as well as an antigen-specific immune response, had only a tendency to increase (10.1 ± 2.0 pg/ml vs 9.1 ± 1.1 pg/ml in the control group, p > 0.05). Against this background, we observed more than 3-fold increase in the level of anti-inflammatory IL-10, which is a product of type 2 helper cells, responsible for the formation of a humoral antigen-specific immune response, — 4.42 ± 1.00 pg/ml vs 1.41 ± 0.59 pg/ml, respectively (p < 0.05). Conclusions. It was found that sickly children had been characterized by the changes of mucosal protection, low content of α-defensins 1–3 in oropharyngeal secretions. The revealed changes indicated the stress of the local defense mechanisms. The investigation has revealed that overproduction of HNP 1–3 in children with recurrent bronchitis against the background of the disturbed balance between pro- and anti-inflammatory cytokines could be one of the causes of recurrent forms of the respiratory tract infection


Keywords


sickly children; recurrent bronchitis; antimicrobial peptides

Full Text:

PDF

References


Surkova ЕА, Bulgakova ТV, Sologub ТS et al. Myeloperoxidase and lactoferrin in patients with cystic fibrosis. Meditsinskaya immunologiya. 2004;1-2:67-74. (In Russian).

Lillard JWJr, Boyaka PN, Chertov O, et al. Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc Natl Acad Sci USA.1999;96(2):651-6. doi: 10.1073/pnas.96.2.651.

Van Wetering S, Mannesse-Lazeroms SPG, Van Sterkenburg MAJA et al. Neutrophil defensins stimulate the release of cytokines by airway epithelial cells: modulation by dexamethasone. Inflamm Res. 2002;51(1):8-15. doi: 10.1007/PL00000282.

Yount NY, Yeaman MR. Immunoconsiluum: Perspectives in Antimicrobial Peptide Mechanisms of Action and Resistance. Protein and Peptide. Letters. 2005:49-67. doi: 10.2174/0929866053405959.

Rinker SD, Trombley MP, Gu X, et al. Deletion of mtrC in Haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the CpxRA regulon. Infection and immunity. 2011;79(6):2324-34. doi: 10.1128/IAI.01316-10.

ZhangL YuW, He T, et al. Contribution of humanα-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science.2002;298:995-1000. doi: 10.1126/science.1076185.

Abaturov АЕ, Herasimenko ON, Vysochina IL, et al. Defenzinyi i defenzin zavisimyie zabolevaniya [Defensins and defensindepending diseases] [bliography]. Odesa: ВМВ; 2011. 265 p. (In Russian).

Shramko SV, Arhipova SV, Bazhenova LG, et al. Diagnostic value of some acute-phase proteins in purulent-inflammatory diseases of the uterine appendages. Byulleten Sibirskoy meditsinyi. 2006;3:112-6. (In Russian).

Baynes RD, Bezwoda WR, Khan O, Mansoor N. Relationship of plasma lactoferrin content to neutrophil regeneration and bone marrow infusion. Scand J Haematol. 1986;36:79-84. doi: 10.1111/j.1600-0609.1986.tb02654.x.

Birgens HS. The biological significance of Lactoferrin in haematology. Scand J Haematol. 1984;33:225-30. doi: 10.1111/j.1600-0609.1984.tb02220.x.

Boronina LG. Mikrobiologicheskie aspektyi infektsiy, vyizvannyih Haemophilus influenzae, u detey [Microbiological aspects of infections caused by Haemophilus influenzae in children] [bibliography]. St. Petersburg; 2007. 38 p. (In Russian).

Bedareva TU, Poponnikova TV, Varhammeva TN. Changes of cytokine status and the level of antimicrobial peptides in tick neuroinfections in children. Sibirskiy meditsinskiy Zhurnal. 2008.7:22-5. (In Russian).

Farnaud S, Evans RW. Lactoferrin - a multifunctional protein with antimicrobial properties. Mol Immunol. 2003; 40(7):395-405. doi: 10.1016/S0161-5890(03)00152-4.

Naidu AS. Lactoferrin: natural, multifunctional, antimicrobial [bibliography]. CRC Press; 2000. 184 p. Available from: https://www.crcpress.com/Lactoferrin-Natural---Multifunctional---Antimicrobial/Naidu/p/book/9780849309090

Anderson B, Baker H, Norris G, Rice D, et al. Structure of human lactoferrin: crystallographic structure analysis and refinement at 2.8 A resolution. J Mol Biol. 1989;209(4):711-34. doi: 10.1016/0022-2836(89)90602-5.

Kokryakov VR, Pygarevskiy VE, Aleshyna GM, Shamova OV. Sinergicheskoe antimikrobnoe deystvie kationnyih belkov pri fagotsitoze [Synergistic antimicrobial action of cationic proteins in phagocytosis]. Sbornik nauchnyh trudov pod redakciey Mayanskogo AN. Gorkiy; 1989. pp. 98-103. (In Russian).

Ellison RT, Giehl TJ, LaForce F. Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin. Infect and Immun. 1988 Nov;56(11):2774-81. PMCID: PMC259649.

Rainard P. Bacteriostatic activity of bovine milk lactoferrin against mastitic bacteria. Vet Microbiol. 1986;11:387-92. doi: 10.1016/0378-1135(86)90068-4.

Van der Strate BW, Beljaars L, Molema Get al. Antiviral activities of lactoferrin. Antiviral Res. 2001;52(3):225-39. doi: 10.1016/S0166-3542(01)00195-4.

Fujihara T, Hayashi K. Lactoferrin inhibits herpes simplex virus type-1 (HSV-1) infection to mouse cornea. Arch Virol. 1995;140(8):1469-72. doi: 10.1007/BF01322673.

Harmsen MC, Swart PJ, De BethuneM P, et al. Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J Infect Dis. 1995;172:280-8. doi: 10.1093/infdis/172.2.380.

Puddu P, Borghi P, Gessani S, et al. Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection.Int. J Biochem Cell Biol. 1998;30(9):1055-62. doi: 10.1016/S1357-2725(98)00066-1.

Sojar HT, Hamada N, Genco RJ. Structures involved in the interaction of Porphyromonas gingivalis fimbriae and human lactoferrin. FEBS Lett. 1998;422:205-8. PMID: 9490007.

Nozaki A, Ikeda M, Naganuma A, et al. Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein. J Biol Chem. 2003;278(12):10162-73. doi: 10.1074/jbc.M207879200.

Lehrer RI, Ganz T. Endogenous vertebrate antibiotics. Defensins, protegrins and other cysteine-rich antimicrobial peptides. Ann N.Y. Acad Sci. 1996;797:228-39. doi: 10.1111/j.1749-6632.1996.tb52963.x.

Giansanti F, Rossi P, Massucci MT et al. Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin. Biochem Cell Biol. 2002;80(1):125-30. doi: 10.1139/o01-208.

Beiter K, Wartha F, Hurwitz R, et al. The Capsule Sensitizes Streptococcus pneumoniae to Defensins Human Neutrophil Proteins 1 to 3 . Infect Immun. 2008;76(8): 3710-6. doi: 10.1128/IAI.01748-07.

Doss M, White MR, Tecle T, Hartshorn KL. Human defensins and LL-37 in mucosal immunity. J Leukoc Biol .2010;87:79-92. doi: 10.1189/jlb.0609382.

Dugan AS, Maginnis MS, Jordan JA et al. Human alpha-Defensins Inhibit BK Virus Infection by Aggregating Virions and Blocking Binding to Host Cells. J Biol Chem. 2008;283(45):31125-32. doi: 10.1074/jbc.M805902200.

Trabattoni D, Caputo SL, Maffeis G, et al. Human alpha defensin in HIV-exposed but uninfected individuals. J Acquir Immune Defic Syndr. 2004;35(5):455-63. PMID: 15021310.

Budikhina AS, Pinegin BV. Defensins are multifunctional human cationic peptides]. Immunopatologiya, allergologiya, infektologiya. 2008;2:31-40. (In Russian).

Kokryakov V.N, Kovalchuk LV, Aleshina GM, Shamova OV. Cationic antimicrobial peptides as molecular immunity factors: multifunctionality. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2006;2:98-105. (In Russian).

Voglis S, Quinn K, Tullis E, et al. Human neutrophil peptides and phagocytic deficiency in bronchiectatic lungs. Am J Respir Crit Care Med. 2009;180(2):159-66. doi: 10.1164/rccm.200808-1250OC.




Copyright (c) 2017 CHILD`S HEALTH

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

 

© Publishing House Zaslavsky, 1997-2018

 

   Seo анализ сайта