Protein Clara trong máu cuống rốn CC16 dự đoán sự phát triển của bệnh dysplasia phế quản phổi

Zeitschrift für Kinderheilkunde - Tập 167 - Trang 1305-1312 - 2008
Alexandra J. J. Schrama1, Alfred Bernard2, Ben J. H. M. Poorthuis3, Aeilko H. Zwinderman4, Howard M. Berger1, Frans J. Walther1
1Neonatal Center, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
2Unit of Industrial Toxicology and Occupational Medicine, Faculty of Medicine, Catholic University of Louvain, Brussels, Belgium
3Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
4Department of Medical Statistics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Tóm tắt

Protein Clara (CC16) là một protein chống viêm và là một dấu hiệu sinh học của tế bào mô phổi và tổn thương màng phế nang - mao mạch ở người lớn. Chúng tôi đã điều tra xem nồng độ CC16 thấp trong máu cuống rốn có liên quan đến sự phát triển của hội chứng suy hô hấp (RDS) và bệnh dysplasia phế quản phổi (BPD) ở trẻ sinh non hay không, cũng như mối quan hệ giữa CC16 và yếu tố đối kháng viêm, enzym phospholipase A2 tiết ra (sPLA2). Nồng độ CC16, hoạt tính sPLA2 và nồng độ IL-6 đã được đo trong huyết tương máu cuống rốn của 79 trẻ sinh non (25 trẻ trong nhóm đối chứng, 37 trẻ phát triển RDS và 17 trẻ phát triển BPD). Sau khi điều chỉnh theo tuổi thai và điểm Apgar tại 5 phút, nồng độ CC16 thấp hơn ở trẻ BPD so với nhóm đối chứng sinh non (p<0.01). Hoạt tính sPLA2 tương tự ở tất cả các nhóm và nồng độ IL-6 tăng lên ở cả trẻ RDS và BPD (p<0.01 và p<0.05, tương ứng, so với nhóm đối chứng). Chúng tôi kết luận rằng nồng độ CC16 thấp trong máu cuống rốn ở trẻ sinh non dự đoán độc lập sự phát triển của BPD. Mức CC16 thấp có thể phản ánh tổn thương phổi giai đoạn đầu, góp phần vào mức độ nghiêm trọng của RDS và tiến triển tới BPD. Cần có các nghiên cứu trong tương lai để đánh giá xem việc cấp phát sớm CC16 tái tổ hợp ở trẻ sinh non có nồng độ CC16 thấp trong máu cuống rốn có ngăn ngừa sự phát triển của BPD hay không.

Từ khóa

#Clara cell protein #BPD #RDS #tiền sản #sinh non #chất chỉ thị sinh học #viêm #phổi

Tài liệu tham khảo

Bernard A, Thielemans N, Lauwerys R, Langhendries JP, Van Lierde M, Freund MM (1994) Clara cell protein in human amniotic fluid: a potential marker of fetal lung growth. Pediatr Res 36:771–775 Bland RD (1972) Cord-blood total protein level as a screening aid for the idiopathic respiratory-distress syndrome. N Engl J Med 287:9–13 Broeckaert F, Clippe A, Knoops B, Hermans C, Bernard A (2000) Clara cell secretory protein (CC16): features as a peripheral lung biomarker. Ann N Y Acad Sci 923:68–77 Brus F, van Oeveren W, Okken A, Oetomo SB (1997) Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome severity. Pediatrics 99:672–680 Chandra S, Davis JM, Drexler S, Kowalewska J, Chester D, Koo HC, Pollack S, Welch R, Pilon A, Levine CR (2003) Safety and efficacy of intratracheal recombinant human Clara cell protein in a newborn piglet model of acute lung injury. Pediatr Res 54:509–515 Crowl RM, Stoller TJ, Conroy RR, Stoner CR (1991) Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. J Biol Chem 266:2647–2651 Dhanireddy R, Kikukawa T, Mukherjee AB (1988) Detection of a rabbit uteroglobin-like protein in human neonatal tracheobronchial washings. Biochem Biophys Res Commun 152:1447–1454 Ferreira PJ, Bunch TJ, Albertine KH, Carlton DP (2000) Circulating neutrophil concentration and respiratory distress in premature infants. J Pediatr 136:466–472 Furue S, Mikawa K, Nishina K, Shiga M, Ueno M, Tomita Y, Kuwabara K, Teshirogi I, Ono T, Hori Y, Matsukawa A, Yoshinaga M, Obara H (2001) Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: correlation with lung surfactant protection. Crit Care Med 29:719–727 Gioldassi XM, Papadimitriou H, Mikraki V, Karamanos NK (2004) Clara cell secretory protein: determination of serum levels by an enzyme immunoassay and its importance as an indicator of bronchial asthma in children. J Pharm Biomed Anal 34:823–826 Groneck P, Götze-Speer B, Oppermann M, Eiffert H, Speer CP (1994) Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates. Pediatrics 93:712–718 Halatek T, Hermans C, Broeckaert F, Wattiez R, Wiedig M, Toubeau G, Falmagne P, Bernard A (1998) Quantification of Clara cell protein in rat and mouse biological fluids using a sensitive immunoassay. Eur Respir J 11:726–733 Harrod KS, Mounday AD, Stripp BR, Whitsett JA (1998) Clara cell secretory protein decreases lung inflammation after acute virus infection. Am J Physiol 275:L924–930 Hermans C, Bernard A (1999) Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med 159:646–678 Hermans C, Knoops B, Wiedig M, Arsalane K, Toubeau G, Falmagne P, Bernard A (1999) Clara cell protein as a marker of Clara cell damage and bronchoalveolar blood barrier permeability. Eur Respir J 13:1014–1021 Hermans C, Petrek M, Kolek V, Weynand B, Pieters T, Lambert M, Bernard A (2001) Serum Clara cell protein (CC16), a marker of the integrity of the air–blood barrier in sarcoidosis. Eur Respir J 18:507–514 Jacobs RF, Wilson CB, Palmer S, Springmeyer SC, Henderson WR, Glover DM, Kessler DL Jr, Murphy JH, Hughes JP, van Belle G, Chi EY, Hodson WA (1985) Factors related to the appearance of alveolar macrophages in the developing lung. Am Rev Respir Dis 131:548–553 Jobe AH (2003) Antenatal factors and the development of bronchopulmonary dysplasia. Semin Neonatol 8:9–17 Johnston CJ, Mango GW, Finkelstein JN, Stripp BR (1997) Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice. Am J Respir Cell Mol Biol 17:147–155 Jorens PG, Sibille Y, Goulding NJ, van Overveld FJ, Herman AG, Bossaert L, De Backer WA, Lauwerys R, Flower RJ, Bernard A (1995) Potential role of Clara cell protein, an endogenous phospholipase A2 inhibitor, in acute lung injury. Eur Respir J 8:1647–1653 Lassus P, Nevalainen TJ, Eskola JU, Andersson S (2000) Clara-cell secretory protein in preterm infants’ tracheal aspirates correlates with maturity and increases in infection. Pediatr Pulmonol 30:466–469 Levine CR, Gewolb IH, Allen K, Welch RW, Melby JM, Pollack S, Shaffer T, Pilon AL, Davis JM (2005) The safety, pharmacokinetics, and anti-inflammatory effects of intratracheal recombinant human Clara cell protein in premature infants with respiratory distress syndrome. Pediatr Res 58:15–21 Loughran-Fowlds A, Oei J, Wang H, Xu H, Wimalasundera N, Egan C, Henry R, Lui K (2006) The influence of gestation and mechanical ventilation on serum clara cell secretory protein (CC10) concentrations in ventilated and nonventilated newborn infants. Pediatr Res 60:103–108 Markarian M, Jackson JJ, Bannon AE (1966) Serial serum total protein values in premature infants with and without the respiratory distress syndrome. J Pediatr 69:1046–1053 Merritt TA, Puccia JM, Stuard ID (1981) Cytologic evaluation of pulmonary effluent in neonates with respiratory distress syndrome and bronchopulmonary dysplasia. Acta Cytol 25:631–639 Miller TL, Shashikant BN, Melby JM, Pilon AL, Shaffer TH, Wolfson MR (2005) Recombinant human Clara cell secretory protein in acute lung injury of the rabbit: effect of route of administration. Pediatr Crit Care Med 6:698–706 Miller TL, Shashikant BN, Pilon AL, Pierce RA, Shaffer TH, Wolfson MR (2006) Effects of an intratracheally delivered anti-inflammatory protein (rhCC10) on physiological and lung structural indices in a juvenile model of acute lung injury. Biol Neonate 89:159–170 Ramsay PL, DeMayo FJ, Hegemier SE, Wearden ME, Smith CV, Welty SE (2001) Clara cell secretory protein oxidation and expression in premature infants who develop bronchopulmonary dysplasia. Am J Respir Crit Care Med 164:155–161 Schrama AJ, de Beaufort AJ, Sukul YR, Jansen SM, Poorthuis BJ, Berger HM (2001) Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study. Acta Paediatr 90:412–416 Touqui L, Arbibe L (1999) A role for phospholipase A2 in ARDS pathogenesis. Mol Med Today 5:244–249 Walsh MC, Szefler S, Davis J, Allen M, Van Marter L, Abman S, Blackmon L, Jobe A (2006) Summary proceedings from the bronchopulmonary dysplasia group. Pediatrics 117:S52–S56 Welty SE (2005) CC10 administration to premature infants: in search of the “silver bullet” to prevent lung inflammation. Pediatr Res 58:7–9 Yedgar S, Cohen Y, Shoseyov D (2006) Control of phospholipase A2 activities for the treatment of inflammatory conditions. Biochim Biophys Acta 1761:1373–1382 Yoon BH, Romero R, Jun JK, Park KH, Park JD, Ghezzi F, Kim BI (1997) 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 177:825–830 Zhang Z, Kundu GC, Yuan CJ, Ward JM, Lee EJ, DeMayo F, Westphal H, Mukherjee AB (1997) Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin. Science 276:1408–1412