Evidence of early systemic activation and transendothelial migration of neutrophils in neonates with severe respiratory distress syndrome

Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study wa...

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Published inPediatric pulmonology Vol. 31; no. 3; pp. 214 - 219
Main Authors Sarafidis, Kosmas, Drossou-Agakidou, Vasiliki, Kanakoudi-Tsakalidou, Florence, Taparkou, Anna, Tsakalidis, Christos, Tsandali, Chaido, Kremenopoulos, Georgios
Format Journal Article
LanguageEnglish
Published New York John Wiley & Sons, Inc 01.03.2001
Wiley-Liss
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ISSN8755-6863
1099-0496
DOI10.1002/ppul.1031

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Abstract Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin‐6 (IL‐6), granulocyte colony‐stimulating factor (G‐CSF), and sL‐selectin using an enzyme‐linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC (P = 0.032), higher expression of the CD11b on neutrophils (P = 0.0065), and higher G‐CSF and IL‐6 plasma levels (P = 0.0047 and P < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL‐selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS. Pediatr Pulmonol. 2001; 31:214–219. © 2001 Wiley‐Liss, Inc.
AbstractList Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin‐6 (IL‐6), granulocyte colony‐stimulating factor (G‐CSF), and sL‐selectin using an enzyme‐linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC (P = 0.032), higher expression of the CD11b on neutrophils (P = 0.0065), and higher G‐CSF and IL‐6 plasma levels (P = 0.0047 and P < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL‐selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS. Pediatr Pulmonol. 2001; 31:214–219. © 2001 Wiley‐Liss, Inc.
Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin‐6 (IL‐6), granulocyte colony‐stimulating factor (G‐CSF), and sL‐selectin using an enzyme‐linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC ( P  = 0.032), higher expression of the CD11b on neutrophils ( P  = 0.0065), and higher G‐CSF and IL‐6 plasma levels ( P  = 0.0047 and P  < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL‐selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS. Pediatr Pulmonol. 2001; 31:214–219. © 2001 Wiley‐Liss, Inc.
Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and sL-selectin using an enzyme-linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC (P = 0.032), higher expression of the CD11b on neutrophils (P = 0.0065), and higher G-CSF and IL-6 plasma levels (P = 0.0047 and P < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL-selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS.
Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and sL-selectin using an enzyme-linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC (P = 0.032), higher expression of the CD11b on neutrophils (P = 0.0065), and higher G-CSF and IL-6 plasma levels (P = 0.0047 and P < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL-selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS.Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and sL-selectin using an enzyme-linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC (P = 0.032), higher expression of the CD11b on neutrophils (P = 0.0065), and higher G-CSF and IL-6 plasma levels (P = 0.0047 and P < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL-selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS.
Author Sarafidis, Kosmas
Drossou-Agakidou, Vasiliki
Tsakalidis, Christos
Tsandali, Chaido
Kremenopoulos, Georgios
Taparkou, Anna
Kanakoudi-Tsakalidou, Florence
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  surname: Kremenopoulos
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Issue 3
Keywords Human
Premature
Lung disease
Respiratory disease
Pathogenesis
Activation
Inflammation
Review
Blood plasma
Newborn diseases
Newborn
Bronchus disease
Complication
Bronchopulmonary dysplasia
Respiratory distress
Neutrophil
Comparative study
Language English
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CC BY 4.0
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Babior B. The respiratory burst of phagocytes. J Clin Invest 1984; 73:599-601.
Wenisch C, Parschalk B, Weiss A, Zedwitz-Liebenstein K, Hahsler B, Wenisch H. High-dose catecholamine treatment decreases polymorphonuclear leukocyte phagocytic capacity and reactive oxygen production. Clin Diagn Lab Immunol 1996; 3:423-428.
Speer CP, Ruess D, Harms K, Herting E, Gefeller O. Neutrophil elastase and acute pulmonary damage in neonates with severe respiratory distress syndrome. Pediatrics 1993; 91:794-799.
Etzioni A. Adhesion molecules-their role in health and disease. Pediatr Res 1996; 39:191-198.
Dale DC, Liles C, Summer WR, Nelson S. Review: granulocyte colony-stimulating factor-role and relationships in infectious diseases. J Infect Dis 1995; 172:1061-1075.
Drossou V, Kanakoudi F, Tzimouli V, Sarafidis K, Taparkou A, Bougiouklis D, Petropoulou T, Kremenopoulos G. Impact of prematurity, stress and sepsis on the neutrophil respiratory burst activity of neonates. Biol Neonate 1997; 72:201-209.
Brus F, van Oeveren W, Okken A, Bambang SO. Activation of circulating polymorphonuclear leukocytes in preterm infants with severe idiopathic respiratory distress syndrome. Pediatr Res 1996; 39:456-463.
Drossou-Agakidou V, Kanakoudi-Tsakalidou F, Sarafidis K, Taparkou A, Tsimouli V, Tsantali H, Kremenopoulos G. Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta 2 integrin expression. Results of a randomized controlled trial. Eur J Pediatr 1998; 157:583-588.
Biffl WL, Moore EE, Moore FA, Barnett CC Jr, Carl VS, Peterson VN. Interleukin-6 delays neutrophil apoptosis. Arch Surg 1996; 131:24-30.
Matsuoka T. A sedative effect of dopamine on the respiratory burst in neonatal polymorphonuclear leukocytes. Pediatr Res 1990; 28:24-27.
Yurdakök M, Gürakan B, Ergin H, Kirazli S. G-CSF and GM-CSF in respiratory distress syndrome. Am J Hematol 1994; 46:155-156.
Brus F, van Oeveren W, Okken A, Octomo SB. Number and activation of circulating polymorphonuclear leukocytes and platelets are associated with neonatal respiratory distress syndrome. Pediatrics 1997; 99:672-680.
Tsao PN, Teng RJ, Tang JR, Yau KI. Granulocyte colony-stimulating factor in the cord blood of premature neonates born to mothers with pregnancy-induced hypertension. J Pediatr 1999; 135:56-59.
Donnelly SC, Haslett C, Dransfield I, Robertson CE, Carter DC, Ross JA, Grant IS, Tedder TF. Role of selectins in development of adult respiratory distress syndrome. Lancet 1994; 344:215-219.
Mature-Bello G, Liles WC, Radella F II, Steinberg KP, Ruzinski JT, Hudson LD, Martin TR. Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating. Crit Care Med 2000; 28:1-7.
Gillan ER, Christensen RD, Suen Y, Ellis R, van de Ven C, Cairo MS. A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. Blood 1994; 84:1427-1433.
Fujita H, Morita I, Murota S. A possible mechanism for vascular endothelial cell injury elicited by activated leukocytes: a significant involvement of adhesion molecules, CD11/CD18, and ICAM-1. Arch Biochem Biophys 1994; 309:62-69.
Contreras M, Hariharan N, Lewandoski JR, Ciesielski W, Koscik R, Zimmerman JJ. Bronchoalveolar oxyradical inflammatory elements herald bronchopulmonary dysplasia. Crit Care Med 1996; 24:29-37.
Johnson JL, Moore EE, Tamura DY, Zallen G, Biffl WL, Silliman CC. Interleukin-6 augments neutrophil cytotoxic potential via selective enhancement of elastase release. J Surg Res 1998; 76:91-94.
Nathan CF. Respiratory burst in adherent human neutrophils: triggering by colony stimulating factors CSF-GM and CSF-G. Blood 1989; 73:301-306.
Weimann E, Rutkowski S, Reisbach G. G-CSF, GM-CSF and IL-6 levels in cord blood: diminished increase of G-CSF and IL-6 in preterms with perinatal infection compared to term neonates. J Perinat Med 1998; 26:211-218.
Källman J, Ekholm L, Eriksson M, Malmström B, Schollin J. Contribution of interleukin-6 in distinguishing between mild respiratory disease and neonatal sepsis in the newborn infant. Acta Paediatr 1999; 88:880-884.
Jackson JC, Chi EY, Wilson CB, Truong WE, The EC, Hodson WA. Sequence of inflammatory cell migration into lung during recovery from hyaline membrane disease in premature newborn monkeys. Am Rev Respir Dis 1987; 135:937-940.
Ikeno K. Increased granulocyte-colony stimulating factor (G-CSF) levels in neonates with perinatal complications. Acta Paediatr Jpn 1994; 36:366-370.
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Chollet-Martin S, Jourdain B, Gilbert C, Elbim C, Chastre J, Gouregot-Posidalo MA. Interaction between neutrophils and cytokines in blood and alveolar spaces during ARDS. Am J Respir Crit Care Med 1996; 154:594-601.
Gessler P, Kirchmann N, Kientsch-Engel R, Haas N, Lasch P, Kachel W. Serum concentration of granulocyte colony-stimulating factor in healthy term and preterm neonates and in those with various diseases including bacterial infections. Blood 1993; 82:3177-3182.
Schleiffenbaum B, Spertini O, Tedder TF. Soluble L-selectin is present in human plasma at high levels and retains functional activity. J Cell Biol 1992; 119:229-238.
Sundell HW, Grogaard J, Rojas J, Gray ME, Mohan P, Brigham KL. Lung vascular permeability changes in lambs with hyaline membrane disease. J Dev Physiol 1989; 12:352-362.
Munshi UK, Niu JO, Siddiq MM, Parlton LA. Elevation of interleukin-8 and interleukin-6 precedes influx of neutrophils in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia. Pediatr Pulmonol 1997; 24:331-336.
Maekawa K, Futami S, Nishidi M, Terada T, Inagawa H, Suzuki S, Ono K. Effects of trauma and sepsis on soluble L-selectin and cell surface expression of L-selectin and CD11b. J Trauma 1998; 44:460-468.
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1998; 26
1996; 39
1997; 83
2000; 28
1995; 37
1993; 82
1995; 58
1997; 24
1999; 45
1999; 88
1994; 46
1993; 91
1995; 19
1998; 157
1993; 1
1995; 172
1994; 84
1998; 44
1989; 73
1989; 74
1994; 344
1984; 73
1990; 116
1997; 72
1987; 135
1989; 12
1997; 99
1997; 77
1992; 131
1990; 28
1994; 36
1992; 119
1999; 135
1996; 154
1996; 131
1992; 20
1996; 24
1998; 76
1998; 75
1994; 93
1996; 3
1998; 78
1994; 309
1994; 7
Kerner B (e_1_2_1_43_2) 1992; 20
Gillan ER (e_1_2_1_26_2) 1994; 84
Wortel CH (e_1_2_1_30_2) 1993; 1
e_1_2_1_41_2
e_1_2_1_22_2
e_1_2_1_45_2
e_1_2_1_23_2
e_1_2_1_44_2
e_1_2_1_20_2
Speer CP (e_1_2_1_16_2) 1993; 91
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e_1_2_1_27_2
e_1_2_1_48_2
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e_1_2_1_46_2
e_1_2_1_28_2
e_1_2_1_29_2
Nathan CF (e_1_2_1_24_2) 1989; 73
e_1_2_1_6_2
e_1_2_1_7_2
e_1_2_1_4_2
e_1_2_1_5_2
Sundell HW (e_1_2_1_18_2) 1989; 12
e_1_2_1_34_2
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e_1_2_1_36_2
e_1_2_1_14_2
e_1_2_1_35_2
Gessler P (e_1_2_1_40_2) 1993; 82
e_1_2_1_19_2
Yuo A (e_1_2_1_11_2) 1989; 74
e_1_2_1_8_2
e_1_2_1_17_2
Groneck P (e_1_2_1_2_2) 1998; 75
e_1_2_1_9_2
e_1_2_1_39_2
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Snippet Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in...
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SubjectTerms Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
brinchopulmonary dysplasia
CD11b
cytokines
Emergency and intensive care: neonates and children. Prematurity. Sudden death
Endothelium, Vascular - physiopathology
granulocyte colony-stimulating factor
Granulocyte Colony-Stimulating Factor - blood
Humans
Infant, Newborn
inflamation
Intensive care medicine
interleukin-6
Interleukin-6 - blood
L-Selectin - blood
Matched-Pair Analysis
Medical sciences
neonates
Neutrophil Activation - physiology
neutrophils
Neutrophils - physiology
Pneumology
Respiratory Burst - physiology
respiratory burst activity
respiratory distress syndrome
Respiratory Distress Syndrome, Newborn - blood
Respiratory Distress Syndrome, Newborn - physiopathology
Respiratory system : syndromes and miscellaneous diseases
sL-selectin
Title Evidence of early systemic activation and transendothelial migration of neutrophils in neonates with severe respiratory distress syndrome
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https://www.ncbi.nlm.nih.gov/pubmed/11276134
https://www.proquest.com/docview/77013283
Volume 31
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