Katlinskaya Y.V.*, Krastelyova I.M.**, Ustinovich Y.A.**, Shilkina E.V.**, Shishko G.A.**, Voytenok N.N.***
The soluble form of interleukin-8 receptor CXCR2 as a marker of an inflammation in perinatal pathology
*State Establishment «Republican Scientific-Practical Center of Transfusiology and Medical Biotechnologies», Minsk, Republic of Belarus
**State Educational Establishment «Belarusian Medical Academy of Post-Graduate Education», Minsk, Republic of Belarus
***Fund of molecular humatology and immunology, Moscow, Russian Federation
Vestnik VGMU. 2015;14(6):70-77.
Abstract.
Objectives. To determine the levels of interleukin-8 soluble receptor CXCR2 (sCXCR2) as a marker of neutrophilic leukocytes involvement in the inflammatory process during the pathology of pregnancy and respiratory distress syndrome (RDS) in premature infants.
Material and methods. Soluble sCXCR2 level in the supernatants of activated neutrophils and human biological fluids was determined by «sandwich» enzyme-linked immunoassay.
Results. Soluble CXCR2 was found in the amniotic fluid in the second trimester in the pathology of pregnancy. The levels of sCXCR2 directly correlated with the levels of soluble tumor necrosis factor y (TNF- ) receptor p55, which can indicate that sCXCR2 is produced by neutrophils in response to the increasing concentration of TNF-) caused by infection. We have also examined the groups of preterm infants with RDS devoid of infectious pathology and with RDS associated with pneumonia, intrauterine infection and sepsis. It has been shown that the levels of sCXCR2 in the urine of newborns on the 1st day after birth were significantly reduced in patients with RDS and infection in comparison with the group of infants with RDS without accompanying infectious pathology.
Conclusions. Thus the levels of sCXCR2 may reflect the severity of inflammatory changes during RDS, and serve as a signal for an early treatment. Moreover, the determination of sCXCR2 in newborns urine is not associated with conducting invasive procedures.
Key words: systemic inflammatory response, infection, amniotic fluid, urine, soluble CXCR2.
References
1. Baggiolini M. Chemokines in pathology and medicine. J Intern Med. 2001 Aug;250(2):91-104.
2. Doroshenko T, Chaly Y, Savitskiy V, Maslakova O, Portyanko A, Gorudko I, Voitenok NN. Phagocytosing neutrophils down-regulate the expression of chemokine receptors CXCR1 and CXCR2. Blood. 2002 Oct;100(7):2668-71.
3. Kotlinskiy KV, Doroshenko TM, Kotlinskaya YuV, Kirkovskiy LV, Sholukh AM, Chalyy YuV, Voytenok NN. Vyiavlenie i immunokhimicheskaia kharakteristika rastvorimoi formy retseptora CXCR2 interleikina-8 cheloveka [ Identification and immunochemical characteristic of a soluble form of a receptor of CXCR2 interleykina-8 person]. Dokl Nats Akad Nauk Belarusi. 2008;52(6):87-92.
4. Kotlinskaya YuV, Kotlinskiy KV, Doroshenko TM, Akalovich ST, Voytenok NN. Rol' metalloproteinaz v reguliatsii ekspressii retseptora interleikina-8 CXCR2 na neitrofilakh cheloveka [A role of metalproteinases in a regulation of an expression of a receptor interleykina-8 CXCR2 on neutrophils of the person]. Dokl Nats Akad Nauk Belarusi. 2011;55(3):83-7.
5. Kotlinskiy KV, Kotlinskaya YuV, Sholukh AM, Akalovich ST, Doroshenko TM, Chalyy YuV, Voytenok NN. Biokhimicheskaia kharakteristika rastvorimoi formy retseptora CXCR2 interleikina-8 cheloveka [Biochemical characteristic of a soluble form of a receptor of CXCR2 interleykina-8 person]. Vestsi NAN Belarusi Ser Biial Navuk. 2009;(2):85-9.
6. Yoon BH, Romero R, Jun JK, Park KH, Park JD, Ghezzi F, Kim BI. Amniotic fluid cytokines (interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8) and the risk for the development of bronchopulmonary dysplasia. Am J Obstet Gynecol. 1997 Oct;177(4):825-30.
7. Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998 Jul;179(1):194-202.
8. Yoon BH, Romero R, Kim KS, Park JS, Ki SH, Kim BI, Jun JK. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol. 1999 Oct;181(4):773-9.
9. Watterberg KL, Demers LM, Scott SM, Murphy S. Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics. 1996 Feb;97(2):210-5.
10. Redl H, Schlag G, Adolf GR, Natmessnig B, Davies J. Tumor necrosis factor (TNF)-dependent shedding of the p55 TNF receptor in a baboon model of bacteremia. Infect Immun. 1995 Jan;63(1):297-300.
11. Kupferminc MJ, Peaceman AM, Aderka D, Wallach D, Peyser MR, Lessing JB, Socol ML. Soluble tumor necrosis factor receptors in maternal plasma and second-trimester amniotic fluid. Am J Obstet Gynecol. 1995 Sep;173(3 Pt 1):900-5.
12. Nashkevich NN, Akalovich S, Louneva N, Heavner GA, Voitenok NN. A monoclonal antibody and an enzyme immunoassay for human Ala-IL-8(77). J Immunol Methods. 2002 Dec;270(1):37-51.
13. Petevka NV, Nashkevich NN, Tikhonov II, Kolesnikova TS, Koleda ST, Butenko SS, Doroshenko TM, Voytenok NN. Immunofermentnyi metod opredeleniia rastvorimogo R55 retseptora FNO cheloveka [Immunoenzymatic method of definition of soluble P55 of a receptor TNF of the person]. V: Klinicheskaia allergologiia i immunologiia. Immunodiagnostika i immunoreabilitatsiia: tr 2-i Mezhdunar konf i 1-go s"ezda BAAKI. Minsk, RB; Vitebsk, RB; 1998. Р. 193–5.
14. Merritt TA, Cochrane CG, Holcomb K, Bohl B, Hallman M, Strayer D, Edwards DK 3rd, Gluck L. Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia. J Clin Invest. 1983 Aug;72(2):656-66.
15. Ogden BE, Murphy SA, Saunders GC, Pathak D, Johnson JD. Neonatal lung neutrophils and elastase/proteinase inhibitor imbalance. Am Rev Respir Dis. 1984 Nov;130(5):817-21.
16. Murch SH, Costeloe K, Klein NJ, Rees H, McIntosh N, Keeling JW, MacDonald TT. Mucosal tumor necrosis factor-alpha production and extensive disruption of sulfated glycosaminoglycans begin within hours of birth in neonatal respiratory distress syndrome. Pediatr Res. 1996 Sep;40(3):484-9.
17. Kotecha S, Chan B, Azam N, Silverman M, Shaw RJ. Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in bronchoalveolar lavage fluid from premature infants who develop chronic lung disease. Arch Dis Child Fetal Neonatal Ed. 1995 Mar;72(2):F90-6.
