Abstract
We have studied activation of circulating polymorphonuclear leukocytes(PMN) in plasma of preterm infants with severe idiopathic respiratory distress syndrome (IRDS group, n = 15) and without IRDS (reference group,n = 15) during the first 5 postnatal days. We have observed lower median PMN counts in the IRDS group than in the reference group from d 2 (1.4× 109/L versus 4.8 × 109/L in the reference group, p < 0.001) to d 4 to 6 (1.6 × 109/Lversus 4.0 × 109/L, p < 0.01). Lower PMN counts in the IRDS infants were accompanied by lower median plasma elastase-α1-proteinase inhibitor (PI) concentrations (53.6 ng/mLversus 128.0 ng/mL in the reference group on d 2, p < 0.05). Simultaneously, median elastase-α1-PI/PMN ratios of these infants were significantly higher (40.8 ng/106 PMN versus 21.8 ng/106 PMN on d 2, p < 0.05), indicating activation of circulating PMN. Activation of circulating PMN in the IRDS group is associated with platelet-activating factor (PAF) release and complement activation from within 6 to 12 h of birth but not with release of tumor necrosis factor-α. PAF release was represented by significantly reduced inhibiting capacity (58% of normal human plasma, p < 0.01) and complement activation by higher median plasma C3a des-Arg concentrations (1680 ng/mL versus 325 ng/mL in the reference group, p < 0.001). We conclude that circulating PMN are activated in preterm infants with severe IRDS, which might be caused by systemic PAF release and complement activation. This activation process may play a role in the pathogenesis of the IRDS by influx of activated PMN into the lungs.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- IRDS:
-
idiopathic respiratory distress syndrome
- BPD:
-
bronchopulmonary dysplasia
- ARDS:
-
adult respiratory distress syndrome
- PMN:
-
polymorphonuclear leukocytes
- α1-PI:
-
α1-proteinase inhibitor
- TNF-α:
-
tumor necrosis factor α
- PAF:
-
platelet-activating factor
- IC:
-
inhibiting capacity of plasma
- Fio2:
-
fractional concentration of inspired O2
- HELLP:
-
hemolysis, elevated liver enzymes, and low platelet count syndrome
References
Ogden BE, Murphy SA, Saunders GC, Pathak D, Johnson JD 1984 Neonatal lung neutrophils and elastase/proteinase inhibitor imbalance. Am Rev Respir Dis 130: 817–821.
Merritt TA, Cochrane CG, Holcomb K, Bohl B, Hallman M, Strayer D, Edwards DK 1983 Elastase and α-1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome.. J Clin Invest 72: 656–666.
Jackson JC, Chi EY, Wilson CB, Truog WE, Teh EC, Hodson WA 1987 Sequence of inflammatory cell migration into the lung during recovery from hyaline membrane disease in premature newborn monkeys. Am Rev Respir Dis 135: 937–940.
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.
Groneck P, Reuss D, Götze-Speer B, Speer CP 1993 Effects of dexamethasone on chemotactic activity and inflammatory mediators in tracheobronchial aspirates of preterm infants at risk for chronic lung disease. J Pediatr 122: 938–944.
Stenmark KR, Eyzaguirre M, Westcott JY, Henson PM, Murphy RC 1987 Potential role of eicosanoids and PAF in the pathophysiology of broncho-pulmonary dysplasia. Am Rev Respir Dis 136: 770–772.
Speer CP, Reuss D, Harms K, Herting E, Gefeller O 1993 Neutrophil elastase and acute pulmonary damage in neonates with severe respiratory distress syndrome. Pediatrics 91: 794–799.
Groneck P, Oppermann M, Speer CP 1993 Levels of complement anaphylatoxin C5a in pulmonary effluent fluid of infants at risk for chronic lung disease and effects of dexamethasone treatment. Pediatr Res 34: 586–590.
Murch SH, MacDonald TT, Wood CBS, Costeloe KL 1992 Tumor necrosis factor in the bronchoalveolar secretions of infants with the respiratory distress syndrome and the effect of dexamethasone treatment. Thorax 47: 44–47.
Murch SH, MacDonald T, Costeloe K 1994 Macrophage-associated chemokines and cytokines in neonatal respiratory distress syndrome. Early Hum Dev 38: 60
Bruce M, Wedig KE, Jentoft N, Martin K, Cheng PW, Boat TF, Fanaroff AA 1985 Altered urinary excretion of elastin cross-links in premature infants who develop bronchopulmonary dysplasia. Am Rev Respir Dis 131: 568–572.
Bruce MC, Schuyler M, Martin RJ, Starcher BC, Tomashefski JF, Wedig KE 1992 Risk factors for the degradation of lung elastic fibers in the ventilated neonate. Am Rev Respir Dis 146: 204–212.
Walti H, Tordet C, Gerbaut L, Sauger P, Moriette G, Relier JP 1989 Persistent elastase/proteinase inhibitor imbalance during prolonged ventilation of infants with bronchopulmonary dysplasia: evidence for the role of nosocomial infections. Pediatr Res 26: 351–355.
Vercelotti GM, Yin HQ, Gustafson KS, Nelson PO, Jacob HS 1988 Platelet-activating factor primes neutrophil responses to agonists: role in promoting neutrophil-mediated endothelial damage. Blood 137: 1364–1370.
Hamaski Y, Mojarad M, Saga T, Tai H, Said SI 1984 Platelet-activating factor raises airway and vascular pressures and induces edema in lungs perfused with platelet-free solution. Am Rev Respir Dis 129: 742–746.
O'Brodovich HM, Coates G 1988 Pulmonary edema in respiratory distress syndrome and bronchopulmonary dysplasia. In: Merritt TA, Northway WH, Boynton BR (eds) Bronchopulmonary Dysplasia. Blackwell Scientific Publications, Boston, 143–159.
Roall JA, Levin DL 1987 Adult respiratory distress syndrome in pediatric patients: I. Clinical aspects, pathophysiology, and mechanisms of lung injury. J Pediatr 112: 169–180.
Sarnaik AP, Lieh-Lai M 1994 Adult respiratory distress syndrome in children. Pediatr Clin North Am 41: 337–364.
Suter PM, Suter S, Girardin E, Roux-Lombard P, Grau GE, Dayer JM 1992 High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis 145: 1016–1022.
Robbins RA, Russ WD, Rasmussen JK, Clayton MM 1987 Activation of the complement system in the adult respiratory distress syndrome. Am Rev Respir Dis 135: 651–658.
Marks JD, Marks CB, Luce JM, Montgomery AB, Turner J, Metz CA, Murray JF 1990 Plasma tumor necrosis factor in patients with septic shock. Mortality rate, incidence of adult respiratory distress syndrome and effects of methyl-prednisolone administration. Am Rev Respir Dis 141: 94–97.
Weinberg PF, Mathay MA, Webster RO, Roskos KV, Goldstein IM, Murray JF 1984 Biologically active products of complement and acute lung injury in patient with the sepsis syndrome. Am Rev Respir Dis 130: 791–796.
Chang SW, Feddersen CO, Henson PM, Voelkel NF 1987 Platelet-activating factor mediates hemodynamic changes and lung injury in endotoxin-treated rats. J Clin Invest 79: 1498–1509.
Giedion A, Haefliger H, Dangel P 1973 Acute pulmonary x-ray changes in hyaline membrane disease treated with artificial ventilation and positive end expiratory pressure. Pediatr Radiol 1: 145–152.
Haeger M, Unander M, Bengtsson A 1991 Complement activation in relation to development of preeclampsia. Obstet Gynecol 78: 46–49.
Propp RA, Alper CA 1968 C3 synthesis in the human fetus and lack of transplacental passage. Science 162: 672–673.
Koenig JM, Christensen RD 1989 Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 321: 557–562.
Jansen NJG, van Oeveren W, van Vliet M, Stoutenbeek CP, Eysman L, Wildevuur Ch RH 1991 The role of different types of corticosteroids in the inflammatory mediators in cardiopulmonary bypass. Eur J Cardiothorac Surg 5: 211–217.
Furukawa M, Lee EL, Johnston JM 1993 Platelet-activating factor-induced ischemic bowel necrosis: the effect of platelet-activating factor acetylhydrolase. Pediatr Res 34: 237–241.
Gu YJ, Obster R, de Haan J, Gallandat Huet RCG, van Oeveren W 1992 Biocompatibility of leukocyte removal filters during bedside leukocyte filtration of red cell concentrates. Transfus Sci 13: 467–472.
Kazatchkine MD, Fearon DT, Metcalfe DD, Rosenberg RD, Austen KF 1982 Structural determinants of the capacity of heparin to inhibit the formation of the human amplification convertase. J Clin Invest 67: 223–228.
Wegmuller E, Kazatchkine MD, Nydegger UE 1983 Complement activation during extracorporeal blood bypass. Plasma Ther Transfus Technol 4: 361–71.
Plotz FB, van Oeveren W, Hultquist KA, Miller C, Bartlett RH, Wildevuur Ch RH 1992 Heparin coated circuits reduce complement activation and release of inflammatory mediators during extracorporeal circulation in rabbits. Artif Organs 16: 366–370.
van Lingen RA, Hofhuis WDJ, Dekker I, Baerts W, Hahlen K, Sauer PJJ 1992 The effect of heparin in arterial catheters on the coagulation in preterm infants. J Perinat Med 20: 39–46.
Plotz FB, van Oeveren W, Bartlett RH, Wildevuur Ch RH 1993 Blood activation during neonatal extracorporeal life support (ECLS). J Thorac Cardiovasc Surg 105: 823–832.
Tracey KJ, Vlassara H, Cerami A 1989 Cachectin/tumor necrosis factor. Lancet 2: 1122–1125.
Rich EA, Panuska JR, Wallis RS, Wolf CB, Leonard ML, Ellner JL 1989 Dyscoordinate expression of tumor necrosis factor- by human blood monocytes and alveolar macrophages. Am Rev Respir Dis 130: 1010–1016.
Prescott SM, Zimmerman GA, McIntyre TM 1990 Platelet-activating factor. J Biol Chem 262: 4215–4222.
Caplan M, Hsueh W, Kelly A, Donovan M 1990 Serum PAF acetylhydrolase increases during neonatal maturation. Prostaglandins 39: 705–714.
Gaylord MS, Smith Z, Lorch V, Blank M, Anderson M, Snyder F 1990 Platelet-activating factor (PAF) levels in premature infants in the first two weeks of life as measured by a new radioimmunoassay (RIA). Pediatr Res 27: 205A
Sun X, Hsueh W 1991 Platelet-activating factor produces shock, in vivo complement activation, and tissue injury in mice. J Immunol 147: 509–514.
Schrod L, Frauendienst-Egger G, Stockhausen von HB, Kirschfink M 1992 Complement fragment C3a in plasma of asphyxiated neonates. Eur J Pediatr 151: 688–692.
Stimler NP, Hugli TE, Bloor CM 1980 Pulmonary injury induced by C3a and C5a anaphylatoxins. Am J Pathol 100: 327–348.
Zilow G, Zilow EP, Burger R, Linderkamp O 1993 Complement activation in newborn infants with early onset infection. Pediatr Res 34: 199–203.
Burger R, Zilow G, Bader A, Friedlein A, Naser W 1988 The C terminus of the anaphylatoxin C3a generated upon complement activation represents a neoantigenic determinant with diagnostic potential. J Immunol 141: 553–558.
de Bont ESJM, Martens A, van Raan J, Samson G, Fetter WPF, Okken A, de Leij LHFM 1993 Tumor necrosis factor-, interleukin-1, and interleukin-6 plasma levels in neonatal sepsis. Pediatr Res 33: 380–383.
Rubin BB, Smith A, Liauw S, Isenman D, Romaschin AD, Walker PM 1990 Complement activation and white cell sequestration in postischemic skeletal muscle. Am J Physiol 259:H525–H531.
MacPhaden AR, Whaley K 1985 The complement system in sepsis and trauma. Br Med Bull 41: 281–286.
Saugstad OD, Buo L, Johansen HT, Roise O, Aasen AO 1992 Activation of the plasma kallikrein-kinin system in respiratory distress syndrome. Pediatr Res 32: 431–435.
Brus F, van Oeveren W, Okken A, Bambang Oetomo S 1994 Activation of the plasma clotting, fibrinolytic and kinin-kallikrein system in preterm infants with severe idiopathic respiratory distress syndrome. Pediatr Res 36: 647–653.
Kaplan AP, Silverberg M 1987 The coagulation-kinin pathway of human plasma. Blood 70: 1–15.
Andrew M, Massicotte-Nolan P, Karpaatkin M 1983 Plasma protease inhibitors in premature infants: influence of gestational age, postnatal age, and health status. Proc Soc Exp Biol Med 173: 495–500.
Caplan MS, Kelly A, Hsueh W 1992 Endotoxin and hypoxia-induced intestinal necrosis in rats: the role of platelet-activating factor. Pediatr Res 31: 428–434.
Wirthmueller U, de Weck AL, Dahinden CA 1989 Platelet-activating factor production in human neutrophils by sequential stimulation with granulocyte macrophage colony-stimulating factor and the chemotactic factors C5a and formyl-methionylleucyl-phenylalanine. J Immunol 142: 3213–3218.
Acknowledgements
The authors thank Johan Haan for his technical assistance and Annalie van der Vijver, M.D., for correction of the manuscript.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brus, F., Van Oeveren, W., Okken, A. et al. Activation of Circulating Polymorphonuclear Leukocytes in Preterm Infants with Severe Idiopathic Respiratory Distress Syndrome. Pediatr Res 39, 456–463 (1996). https://doi.org/10.1203/00006450-199603000-00013
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199603000-00013
This article is cited by
-
Heart rate and leukocytes after air and ground transportation in artificially ventilated neonates: a prospective observational study
Intensive Care Medicine (2009)
-
Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant
Respiratory Research (2007)
-
Activatie van plasma-eiwitten en bloedcellen bij het neonataal respiratoir distress-syndroom: pathogenetische en therapeutische aspecten
Tijdschrift voor kindergeneeskunde (2000)


