Skip to main content

Advertisement

SpringerLink
Log in

Dysfunction of innate immunity and associated pathology in neonates

  • Symposium: Neonatology — III Evidence and Experience in Neonatal Medicine
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The neutrophils and complement system are the critical elements of innate immunity mainly due to participation in the first line of defense against microorganisms by means of phagocytosis, lysis of bacteria, and activation of naive B-lymphocytes. In this report we provide an overview of the up to date information regarding the neutrophil and complement system’s functional ability in newborn infants in association with the maternal conditions that exist during the intrauterine stage, gestational age and post-neonatal pathology. The neonates’ capacity to control the neutrophil and complement protein activation process has also been discussed because of the evidence that uncontrolled activation of these immune elements provides a significant contribution to the tissue damage and subsequent pathology. The authors are confident that despite the many unanswered questions this review updates their knowledge and points the need for further research to clarify the role of the age-associated dysfunction of neutrophils and complement system in the infection and inflammation related pathology of newborn infants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Marodi L. Neonatal innate immunity to infectious agents. Infect Immun 2006; 74: 1999–2006.

    Article  PubMed  CAS  Google Scholar 

  2. Burg ND, Pillinger MH. The neutrophil: function and regulation in innate and humoral immunity. Clin Immunol 2001; 99: 7–17.

    Article  PubMed  CAS  Google Scholar 

  3. Zilow EP, Hauck W, Linderkamp O, Zilow G. Alternative pathway activation of the complement system in preterm infants with early onset infection. Pediatr Res 1997; 41: 334–339.

    Article  PubMed  CAS  Google Scholar 

  4. Mathison RD, Befus AD, Davison JS, Woodman RC. Modulation of neutrophil function by the tripeptide feG. BMC Immunol 2003; 4: 3–17.

    Article  PubMed  Google Scholar 

  5. Hayashi F, Means TK, Luster AD. Toll-like receptors stimulate human neutrophil function. Blood 2003; 102: 2660–2669.

    Article  PubMed  CAS  Google Scholar 

  6. Segal AW. Structure of the NADPH-oxidase: membrane components. Immunodeficiency 1993; 4: 167–179.

    PubMed  CAS  Google Scholar 

  7. Cowell RM, Plane JM, Silverstein FS. Complement Activation Contributes to Hypoxic-Ischemic Brain Injury in Neonatal Rats. J Neuroscie 2003; 23: 9459–9468.

    Google Scholar 

  8. Palis J, Yoder MC. Yolk-sac hematopoiesis: the first blood cells of mouse and man. Exp Hematol 2001; 29: 927–936.

    Article  PubMed  CAS  Google Scholar 

  9. Tavian M, Robin C, Coulombel L, Peault B. The human embryo, but not its yolk sac, generates lympho-myeloid stem cells: mapping multipotent hematopoietic cell fate in intraembryonic mesoderm. Immunity 2001; 15: 487–495.

    Article  PubMed  CAS  Google Scholar 

  10. Migliaccio G, Migliaccio AR, Petti S, Mavilio F, Russo G, Lazzaro D, Testa U, Marinucci M, Peschle C. Human embryonic hemopoiesis: kinetics of progenitors and precursors underlying the yolk sac-liver transition. J Clin Invest 1986; 78: 51–60.

    Article  PubMed  CAS  Google Scholar 

  11. Robin C, Ottersbach K, de Bruijn M, Ma X, van der Horn K, Dzierzak E. Developmental origins of hematopoietic stem cells. Oncol Res 2003; 13: 315–321.

    PubMed  CAS  Google Scholar 

  12. Palis J, Yoder MC. Yolk-sac hematopoiesis: the first blood cells of mouse and man. Exp Hematol 2001; 29: 927–936.

    Article  PubMed  CAS  Google Scholar 

  13. Kelemen E, Calvo W, Fleidner TM. Atlas of human hemopoietic development, New York: Springer-Verlag; 1979

    Google Scholar 

  14. Koenig JM, Christensen RD. Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 1989; 321: 557–562.

    Article  PubMed  CAS  Google Scholar 

  15. Koenig JM, Christensen RD. The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. Am J Obstet Gynecol 1991; 165: 467–473.

    PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Kocherlakota P, La Gamma EF. Preliminary report: rhG-CSF may reduce the incidence of neonatal sepsis in prolonged preeclampsia-associated neutropenia. Pediatrics 1998; 102: 1107–1011.

    Article  PubMed  CAS  Google Scholar 

  18. Speer CP, Johnston RB Jr. Neutrophil function in newborn infants. In Pollin RA, Fox WW, eds. Fetal and Neonatal Physiology. Philadelphia; Pa: WB Saunders; 1998; 1954–1960.

    Google Scholar 

  19. Koenig JM, Chegini N. Enhanced expression of Fas-associated proteins in decidual and trophoblastic tissues in pregnancy-induced hypertension. Am J Reprod Immunol 2000; 44: 347–349.

    Article  PubMed  CAS  Google Scholar 

  20. Kuntz TB, Christensen RD, Stegner J, Duff P, Koenig JM. Fas and Fas ligand expression in maternal blood and in umbilical cord blood in preeclampsia. Pediatr Res 2001; 50: 743–749.

    Article  PubMed  CAS  Google Scholar 

  21. Bux J, Jung KD, Kauth T, Mueller-Eckhardt C. Serological and clinical aspects of granulocyte antibodies leading to alloimmune neonatal neutropenia. Transfus Med 1992; 2: 143–149.

    PubMed  CAS  Google Scholar 

  22. Rodwell RL, Gray PH, Taylor KM, Minchinton R. Granulocyte colony stimulating factor treatment for alloimmune neonatal neutropenia. Arch Dis Child Fetal Neonatal Ed. 1996; 75: F57–58.

    CAS  Google Scholar 

  23. Lapolla A, Sanzari MC, Zancanaro F, Masin M, Guerriero A, Piva I, Toniato R, Erle G, Plebani M, Fedele D. A study on lymphocyte subpopulation in diabetic mothers at delivery and in their newborn. Diabetes Nutr Metab 1999; 12: 394–399.

    PubMed  CAS  Google Scholar 

  24. Mohandes AE, Touraine JL, Osman M, Salle B. Neutrophil chemotaxis in infants of diabetic mothers and in preterms at birth. J Clin Lab Immunol 1982; 8: 117–120.

    PubMed  CAS  Google Scholar 

  25. Mehta R, Petrova A. Neutrophil Function in Neonates Born to Gestational Diabetic Mothers. J Perinatol 2005; 25: 178–181.

    Article  PubMed  Google Scholar 

  26. Mehta R, Petrova A. Intrapartum Magnesium Sulfate Exposure Attenuates Neutrophil Function in Preterm Neonates. Biol Neonate 2006; 89: 99–103.

    Article  PubMed  CAS  Google Scholar 

  27. Mehta R, Petrova A. Intrauterine neutrophil activation is associated with pulmonary haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2006;91:F415–418.

    Article  CAS  Google Scholar 

  28. Richani K, Soto E, Romero R, Espinosa J, Chaiworapongsa T, Nien JK, Edwin S, Kim YM, Hong JS, Mazor M. Normal Pregnancy is characterized by systemic activation of the complement system. J Matern Fetal Neonatal Med 2005; 17: 239–245.

    Article  PubMed  CAS  Google Scholar 

  29. Jarvis JN, Moore HT, Fine N, Berry SM. Expression of complement regulatory proteins on fetal blood cells in utero. Biol Neonate 1996; 69: 225–229.

    Article  PubMed  CAS  Google Scholar 

  30. Tedesco F, Narchi G, Radillo O, Meri S, Ferrone S, Betterle C. Susceptibility of human trophoblast to killing by human complement and the role of the complement regulatory proteins. J Immunol 1993; 151: 1562–1570.

    PubMed  CAS  Google Scholar 

  31. Holers VM, Girardi G, Mo L, Guthridge JM, Molina H, Pierangeli SS, Espinola R, Xiapwei LE, Mao D, Vialpando CG, Salmon JE. Complement C3 activation is required for antiphospholipid antibody-induced fetal loss. J Exp Med 2002; 2: 211–220.

    Article  Google Scholar 

  32. Soto E, Romero R, Richani K, Espinoza J, Nien JK, Chaiworapongsa T, Santolaya-Forgras J, Edwin SS, Mazor M. Anaphylatoxins in preterm and term labor. J Perinatal Med 2005; 33: 306–313.

    Article  CAS  Google Scholar 

  33. Elimian A, Figueroa R, Canterino J, Verma U, Aguero-Rosenfeld M, Tejani N. Amniotic fluid complement C3 as a marker of intra-amniotic infection. Obstet Gynecol 1998; 92: 72–76.

    Article  PubMed  CAS  Google Scholar 

  34. Tashima LS, Millar LK, Bryant-Greenwood GD. Genes upregulated in human fetal membranes by infection or labor. Obstet Gynecol 1999; 94: 441–449.

    Article  PubMed  CAS  Google Scholar 

  35. Manroe BL, Weinberg AG, Rosenfeld CR, Browne R. The neonatal blood count in health and disease: I. Reference values for neutrophilic cells. J Pediatr 1979; 95: 89–99.

    Article  PubMed  CAS  Google Scholar 

  36. Geissler K, Geissler W, Hinterberger W, Lechner K, Wurnig P. Circulating committed and pluripotent haemopoietic progenitor cells, in infants. Acta Haematol 1986;75:18–22.

    PubMed  CAS  Google Scholar 

  37. Christensen RD, Hill HR, Rothstein G. Granulocytic stem cell (CFUc) proliferation in experimental group B streptococcal sepsis. Pediatr Res 1983; 17: 278–280.

    Article  PubMed  CAS  Google Scholar 

  38. Koenig JM, Luttge B, Benson NA, Christensen RD. Cell cycle status of CD34 + cells in human fetal bone marrow. Early Hum Dev 2001; 65: 159–163.

    Article  PubMed  CAS  Google Scholar 

  39. Mouzinho A, Rosenfeld CR, Sanchez PJ, Risser R. Revised reference ranges for circulating neutrophils in very-low-birth-weight neonates. Pediatrics 1994; 94: 76–82.

    PubMed  CAS  Google Scholar 

  40. Crockett M. Physiology of the neonatal immune system. J Obstetr Gynecol Neonatal Nur 1995; 24: 627–634.

    Article  CAS  Google Scholar 

  41. Sonntag J, Brandenburg U. Polzehl D, Strauss E, Vogel E. Dudenhausen JW, Obladen M. Complement system in healthy term newborns: reference values in umbilical cord blood. Pediatr Dev Pathol 1998; 1: 131–135.

    Article  PubMed  CAS  Google Scholar 

  42. Huffaker J, Witkin SS, Cutler L, Druzin ML, Ledger WJ. Total complement activity in maternal sera, amniotic fluids and cord sera in women with premature labor, preterm rupture of membranes or chorioamnionitis. Surg Gynecol Obstet 1989; 168: 397–401.

    PubMed  CAS  Google Scholar 

  43. Schelonka RL, Infante AJ. Neonatal immunology. Semin Perinatol 1998; 22: 2–14.

    Article  PubMed  CAS  Google Scholar 

  44. Davies J, Turner M, Klein N. The role of the collectin system in pulmonary defense. Paediatr Respir Rev 2001; 2: 70–75.

    Article  PubMed  CAS  Google Scholar 

  45. Watford W, Wright JR, Hester CG, Jiang H, Frank MM. Surfactant protein A regulates complement activation. J Immunol 2001; 167: 6593–6600.

    PubMed  CAS  Google Scholar 

  46. Petrova A, Hanna N, Mehta R. Gestational age related maternal-fetal-neonatal humoral immunity. J Applied Research 2004; 4: 44–49.

    Google Scholar 

  47. Zilow EP, Hauck W, Linderkamp O, Zilow G. Alternative pathway activation of the complement system in preterm infants with early onset infection. Pediatr Res 1997; 41: 334–339.

    Article  PubMed  CAS  Google Scholar 

  48. Miyano A, Nakayama M, Fujita T, Kitajima H, Imai S, Shimizu A. Complement activation in fetuses: assessment by the levels of complement components and split products incord blood. Diagn Immunol 1987; 5: 320–327.

    Google Scholar 

  49. Petrova A, Mehta R. Innate Immunity in Mothers and their Newborn Infants during Preterm Premature Rupture of Membranes. J Applied Research 2005; 5: 282–288.

    Google Scholar 

  50. Christensen RD. Developmental changes in pluripotent hematopoietic progenitors. Early Hum Dev 1988; 16: 195–205.

    Article  PubMed  CAS  Google Scholar 

  51. Mease AD. Tissue neutropenia: the newborn neutrophil in perspective. J Perinatol 1990; 10: 55–59.

    PubMed  CAS  Google Scholar 

  52. Cairo MS, Rucker R, Bennetts GA, Hicks D, Worcester C, Amlie R, Johnson S, Katz J. Improved survival of newborns receiving leukocyte transfusions for sepsis. Pediatrics 1984; 74: 887–892.

    PubMed  CAS  Google Scholar 

  53. Christensen RD, Rothstein G. Exhaustion of mature marrow neutrophils in neonates with sepsis. J Pediatr 1980; 96: 316–318.

    Article  PubMed  CAS  Google Scholar 

  54. Baley JE, Stork EK, Warkentin PI, Shurin SB. Neonatal neutropenia. Am J Dis Child 1988; 142: 1161–1166.

    PubMed  CAS  Google Scholar 

  55. Anderson DC, Abbassi O, Kishimoto TK, Koenig JM, McIntire LV, Smith CW. Diminished lectin-, epidermal growth factor-, complement binding domain-cell adhesion molecule-1 on neonatal neutrophils underlies their impaired CD18-independent adhesion to endothelial cells in vitro. J Immunol 1991; 146: 3372–3379.

    PubMed  CAS  Google Scholar 

  56. Abughali N, Berger M, Tosi MF. Deficient total cell content of CR3 (C11b) in neonatal neutrophils. Blood 1994; 83: 1086–1092.

    PubMed  CAS  Google Scholar 

  57. Ramamoorthy C, Kovarik WD, Winn RK, Harlan JM, Sharar SR. Neutrophil adhesion molecule expression is comparable in perinatal rabbits and humans. Anesthesiology 1997; 86: 420–427.

    Article  PubMed  CAS  Google Scholar 

  58. Christensen RD. Neutrophil kinetics in the fetus and neonate. Am J Pediatr Hematol Oncol 1989; 11: 215–223.

    PubMed  CAS  Google Scholar 

  59. al-Mulla ZS, Christensen RD. Neutropenia in the neonate. Clin Perinatol 1995;22: 711–739.

    PubMed  CAS  Google Scholar 

  60. Carr R. Neutrophil production and function in newborn infants. Br J Haematol 2000; 110: 18–28.

    Article  PubMed  CAS  Google Scholar 

  61. Anderson DC. Neonatal neutrophil dysfunction. Am J Pediatr Hematol Oncol 1989; 11: 224–226.

    PubMed  CAS  Google Scholar 

  62. Christensen RD. Granulocytopoiesis in the neonate and fetus. Trans Med Rev 1990; 4: 8–13.

    CAS  Google Scholar 

  63. Kapur R, Yoder MC, Polin RA. Developmental immunology. In Fanaroff AA, Martin RJ, eds. Neonatal-perinatal medicine St. Louis: Mosby; 2001. p. 676–706.

    Google Scholar 

  64. Lewis DB, Wilson CB. Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In Remington JS, Klein JO, eds. Infectious diseases of the fetus and newborn infant. Philadelphia: W.B. Saunders, 2001; 25–138.

    Google Scholar 

  65. Kim SK, Keeney SE, Alpard SK, Schmalstieg FC. Comparison of L-selectin and CD11b on neutrophils of adults and neonates during the first month of life. Pediatr Res 2003; 53: 132–136.

    PubMed  CAS  Google Scholar 

  66. Graf JM, Smith CW, Mariscalco MM. Contribution of LFA-1 and Mac-1 to CD18-dependent neutrophil emigration in a neonatal rabbit model. J Appl Physiol 1996; 80: 1984–1992.

    PubMed  CAS  Google Scholar 

  67. Anderson DC, Freeman KL, Heerdt B, Hughes BJ, Jack RM, Smith CW. Abnormal stimulated adherence of neonatal granulocytes: impaired induction of surface Mac-1 by chemotactic factors or secretagogues. Blood 1987;70: 740–750.

    PubMed  CAS  Google Scholar 

  68. Anderson DC, Springer TA. Leukocyte adhesion deficiency: an inherited defect in the Mac-1, LFA-1, and p150,95 glycoproteins. Annu Rev Med 1987; 38: 175–194.

    Article  PubMed  CAS  Google Scholar 

  69. Koenig JM, Baron S, Luo D, Benson NA, Deisseroth AB. L-selectin expression enhances clonogenesis of CD34 + cord blood progenitors. Pediatr Res 1999; 45: 867–870.

    Article  PubMed  CAS  Google Scholar 

  70. Rebuck N, Gibson A, Finn A. Neutrophil adhesion molecules in term and premature infants: normal or enhanced leucocyte integrins but defective L-selectin expression and shedding. Clin Exp Immunol 1995; 101: 183–189.

    Article  PubMed  CAS  Google Scholar 

  71. Koenig JM, Simon J, Anderson DC, Smith E, Smith CW. Diminished soluble and total cellular L-selectin in cord blood is associated with its impaired shedding from activated neutrophils. Pediatr Res 1996; 39: 616–621.

    Article  PubMed  CAS  Google Scholar 

  72. Manroe BL, Weinberg AG, Rosenfeld CR, Browne R. The neonatal blood count in health and disease: I. Reference values for neutrophilic cells. J Pediatr 1979; 95: 89–98.

    Article  PubMed  CAS  Google Scholar 

  73. Kim SK, Keeney SE, Alpard SK, Schmalstieg FC. Comparison of L-selectin and CD11b on neutrophils of adults and neonates during the first month of life. Pediatr Res 2003; 53: 132–136.

    PubMed  CAS  Google Scholar 

  74. Weinberger B, Laskin DL, Mariano TM, Sunil VR, DeCoste CJ, Heck DE, Gardner CR, Laskin JD. Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants. J Leukoc Biol 2001; 70: 969–976.

    PubMed  CAS  Google Scholar 

  75. Harris MC, Shalit M, Southwick FS. Diminished actin polymerization by neutrophils from newborn infants. Pediatr Res 1993; 33: 27–31.

    Article  PubMed  CAS  Google Scholar 

  76. Meade VM, Barese CN, Kim C, Njinimbam CG, Marchal CC, Ingram DA, Clapp DW, Dinauer MC, Yoder MC. Rac2 concentrations in umbilical cord neutrophils. Biol Neonate 2006; 90: 156–159.

    Article  PubMed  CAS  Google Scholar 

  77. Glasner A, Egger G, Winter R. Impaired whole-blood polymorphonuclear leukocyte migration as a possible predictive marker for infections in preterm premature rupture of membranes. Infect Dis Obstet Gynecol 2001; 9: 227–232.

    Article  PubMed  CAS  Google Scholar 

  78. Baker CJ, Rench MA, Noya FJ, Garcia-Prats JA. Role of intravenous immunoglobulin in prevention of late-onset infection in low-birth-weight neonates. The Neonatal IVIG Study Group. Rev Infect Dis 1990; 12: S463–468.

    PubMed  Google Scholar 

  79. Dyke MP, Forsyth KD. Plasma fibronectin levels in extremely preterm infants in the first 8 weeks of life. J Paediatr Child Health 1994; 30: 36–39.

    PubMed  CAS  Google Scholar 

  80. Kallman J, Schollin J, Schalen C, Erlandsson A, Kihlstrom E. Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates. Arch Dis Child Fetal Neonatal Ed 1998; 78: F46–50.

    PubMed  CAS  Google Scholar 

  81. Summerfield JA, Sumiya M, Levin M et al. Association of mutations in mannose binding protein gene with childhood infection in consecutive hospital series. BMJ 1997; 314: 1229–1232.

    PubMed  CAS  Google Scholar 

  82. Super M, Thiel S, Lu J, Levinsky RJ, Turner MW. Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet 1989; 2: 1236–1239.

    Article  PubMed  CAS  Google Scholar 

  83. Lewis DB, Wilson CB. Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In Remington JS, Klein JO, eds. Infectious diseases of the fetus and newborn infant Philadelphia: W.B. Saunders, 2001; 25–138.

    Google Scholar 

  84. Hill HR. Biochemical, structural and functional abnormalities of polymorphonuclear leukocytes in the neonate. Pediatr Res 1987; 22: 375–382.

    Article  PubMed  CAS  Google Scholar 

  85. Kjeldsen L, Sengelov H, Lollike K, Borregaard N. Granules and secretory vesicles in human neonatal neutrophils. Pediatr Res 1996; 40: 120–129.

    Article  PubMed  CAS  Google Scholar 

  86. Levy O, Martin S, Eichenwald E, Ganz T, Valore E, Carroll SF, Lee K, Goldmann D, Thorne GM. Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein. Pediatrics 1999; 104: 1327–1333.

    Article  PubMed  CAS  Google Scholar 

  87. Clifford CB, Slauson DO, Neilsen NR, Suyemoto MM, Zwahlen RD, Schlafer DH. Ontogeny of inflammatory cell responsiveness. Inflammation 1989; 13: 221–231

    Article  PubMed  CAS  Google Scholar 

  88. Parry MF, Root RK, Metcalf JA, Delaney KK, Kaplow LS, Richar WJ. Myeloperoxidase deficiency: prevalence and clinical significance. Ann Intern Med 1981; 95: 293–301.

    PubMed  CAS  Google Scholar 

  89. Lakshman R, Finn A. Neutrophil disorders and their management. Clin Pathol 2001; 54: 7–19.

    Article  CAS  Google Scholar 

  90. Molloy EJ, O’Neill AJ, Doyle BT, Grantham JJ, Taylor CT, Sheridan-Pereira M, Fitzpatrick JM, Webb DW, Watson RW. Effects of heat shock and hypoxia on neonatal neutrophil lipopolysaccharide responses: altered apoptosis, Toll-like receptor-4 and CD11b expression compared with adults. Biol Neonate 2006; 90: 34–39.

    Article  PubMed  CAS  Google Scholar 

  91. Oei J, Lui K, Wang H, Henry R. Decreased neutrophil apoptosis in tracheal fluids of preterm infants at risk of chronic lung disease. Arch Dis Child Fetal Neonatal Ed 2003; 88: F245–249.

    Article  PubMed  CAS  Google Scholar 

  92. Kotecha S, Mildner RJ, Prince LR, Vyas JR, Currie AE, Lawson RA, Whyte MK. The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants. Thorax 2003; 58: 961–967.

    Article  PubMed  CAS  Google Scholar 

  93. Burg ND, Pillinger MH. The neutrophil: function and regulation in innate and humoral immunity. Clin Immunol 2001; 99: 7–17.

    Article  PubMed  CAS  Google Scholar 

  94. Haslett C. Granulocyte apoptosis and inflammatory disease. Br Med Bull 1997; 53: 669–683.

    PubMed  CAS  Google Scholar 

  95. Haslett C. Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med 1999; 160: S5–S11.

    PubMed  CAS  Google Scholar 

  96. Speer CP. New insights into the pathogenesis of pulmonary inflammation in preterm infants. Biol Neonate 2001; 79: 205–209.

    Article  PubMed  CAS  Google Scholar 

  97. Dransfield I, Stocks SC, Haslett C. Regulation of cell adhesion molecule expression and function associated with neutrophil apoptosis. Blood 1995; 85: 3264–3673.

    PubMed  CAS  Google Scholar 

  98. Allgaier B, Shi M, Luo D, Koenig JM. Spontaneous and Fasmediated apoptosis are diminished in umbilical cord blood neutrophils compared with adult neutrophils. J Leukoc Biol 1998; 64: 331–336.

    PubMed  CAS  Google Scholar 

  99. Luo D, Schowengerdt Jr KO, Stegner JJ, May Jr WS, Koenig JM. Decreased functional caspase-3 expression in umbilical cord blood neutrophils is linked to delayed apoptosis. Pediatr Res 2003; 53: 859–864.

    Article  PubMed  CAS  Google Scholar 

  100. Koenig JM, Stegner JJ, Schmeck AC, Saxonhouse MA, Kenigsberg LE. Neonatal neutrophils with prolonged survival exhibit enhanced inflammatory and cytotoxic responsiveness. Pediatr Res 2005; 57: 424–429.

    Article  PubMed  CAS  Google Scholar 

  101. Stegner JJ, Schmeck A, Kenigsberg L, Saxonhouse M, Koenig JM. Umbilical cord blood neutrophils with prolonged survival retain their capacity to elaborate reactive oxygen intermediates. Pediatr Res 2004; 55: 390A.

    Google Scholar 

  102. Yasumatsu R, Altiok O, Benarafa C, Yasumatsu C, Bingol-Karakoc G, Remold-O’Donnell E, Cataltepe S. SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 2006; 291: L619–627.

    Article  PubMed  CAS  Google Scholar 

  103. Castellheim A, Pharo A, Fung M, Saugstad OD, Mollnes TE. Complement C5a is a key mediator of meconium-induced neutrophil activation. Pediatr Res 2005; 57: 242–247.

    Article  PubMed  CAS  Google Scholar 

  104. Lassiter HA. Complement factor 9 deficiency in serum of human neonates. J Infect Dis 1992; 166: 53–57.

    PubMed  CAS  Google Scholar 

  105. Hogasen AK, Overlie I, Hansen TW, Abrahamsen TG. Finne PH, Hogasen K. The analysis of the complement activation product SC5b9 is applicable in neonates in spite of their profound C9 deficiency. J Perinat Med 2000; 28: 39–48.

    Article  PubMed  CAS  Google Scholar 

  106. Turker G, Koksal N. Complement 4 levels as early predictors of poor response to surfactant therapy in respiratory distress syndrome. Am J Perinatol 2005; 22: 149–154.

    Article  PubMed  Google Scholar 

  107. Watford WT, Wright JR, Hester CG, Jiang H, Frank MM. Surfactant protein A regulates complement activation. J Immunol 2001; 167: 6593–6600.

    PubMed  CAS  Google Scholar 

  108. Lindenskov PH, Castellheim A, Aamodt G, Saugstad OD. Mollnes TE. Complement activation reflects severity of meconium aspiration syndrome in newborn pigs. Pediatr Res 2004; 56: 810–817.

    Article  PubMed  CAS  Google Scholar 

  109. Miyano A, Kitajima H, Fujiwara F, Nakayama M, Fujita T, Fujimura M, Takeuchi T, Shimizu A. Complement function and the synthesis of lung surfactant may be a regulation which preterm infants have in common. Complement Inflamm 1991; 8: 320–327.

    PubMed  CAS  Google Scholar 

  110. Hecke F, Hoehn T, Strauss E, Obladen M, Sonntag J. In-vitro activation of complement system by lactic acidosis in newborn and adults. Mediators Inflamm 2001; 10: 27–31.

    PubMed  CAS  Google Scholar 

  111. Sonntag J, Wagner MH, Strauss E, Obladen M. Complement and contact activation in term neonates after fetal acidosis. Arch Dis Child Fetal Neonatal Ed 1998; 78: F125–F128.

    Article  PubMed  CAS  Google Scholar 

  112. Frank MM, Miletic VD, Jiang H. Immunoglobulin in the control of complement action. Immunol Res 2000; 22: 137–146.

    Article  PubMed  CAS  Google Scholar 

  113. Zilow G, Zilow EP, Burger R, Linderkamp O. Complement activation in newborn infants with early onset infection. Pediatr Res 1993; 34: 199–203.

    Article  PubMed  CAS  Google Scholar 

  114. Lassiter A. The role of complement in neonatal hypoxicischemic cerebral injury. Clin Perinatol 2004; 31: 117–127.

    Article  PubMed  CAS  Google Scholar 

  115. Schultz SJ, Aly H, Hasanen BM, Khashaba MT, Lear SC, Bendon RW, Gordon LE, Feldholff PW, Lassiter HA. Complement component 9 activation, consumption and neuronal deposition in the post-hypoxic-ischemic central nervous system of human newborn infants. Neurosci Lett 2005; 378: 1–6.

    Article  PubMed  CAS  Google Scholar 

  116. Miletic VD, Frank MM. Complement-immunoglobulin interactions. Curr Opin Immunol 1995; 7: 41–47.

    Article  PubMed  CAS  Google Scholar 

  117. Landor M. Maternal-fetal transfer of immunoglobulins. Ann Immunol 1995; 74: 279–283.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, MEB 238, UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, New Brunswick, New Jersey, 08903-0019, USA

    Anna Petrova &  Rajeev Mehta (Associate Professor of Pediatrics)

Authors
  1. Anna Petrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajeev Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajeev Mehta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petrova, A., Mehta, R. Dysfunction of innate immunity and associated pathology in neonates. Indian J Pediatr 74, 185–191 (2007). https://doi.org/10.1007/s12098-007-0013-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-007-0013-2

Key words

Search

Navigation