Vitamin D(3) induces expression of human cathelicidin antimicrobial peptide 18 in newborns.

Yuka Misawa, Atsushi Baba, Susumu Ito, Miyuki Tanaka, Masaaki Shiohara
Author Information
  1. Yuka Misawa: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
  2. Atsushi Baba: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
  3. Susumu Ito: Research Center for Human and Environmental Sciences, Division of Instrumental Analysis, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
  4. Miyuki Tanaka: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
  5. Masaaki Shiohara: Department of Pediatrics, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan. shiohara@shinshu-u.ac.jp.

Abstract

Bactericidal activities of neutrophils occur by two distinctive mechanisms that are oxygen-dependent and -independent. Human cathelicidin antimicrobial peptide 18 (hCAP18), also known as LL-37/FALL-39, is a neutrophil-specific granule protein. We compared the content of hCAP18 and neutrophil gelatinase-associated lipocalin (NGAL), another neutrophil-specific granule protein, in neutrophils of both neonates and adults by flow cytometry. The percentage as well as fluorescence intensity ratio of hCAP18 and NGAL expression in neonate neutrophils were significantly lower than in adults. Expression of hCAP18 in monocytes, however, was not significantly different between neonates and adults. Both hCAP18 and NGAL expression increased in an age-dependent fashion. Plasma concentration of these peptides measured by enzyme-linked immunosorbent assay was not significantly different between neonates and adults. Oral intake of 1alpha hydroxy vitamin D(3) (1alpha(OH)D(3)) in rickets patients for 4 weeks significantly increased hCAP18 expression in neutrophils compared to age-matched healthy controls without 1alpha(OH)D(3), indicating the potential of vitamin D(3) as a regulator of the innate immune response of neonates.

References

  1. Eur J Haematol. 1997 Mar;58(3):137-53 [PMID: 9150707]
  2. Curr Protein Pept Sci. 2005 Feb;6(1):35-51 [PMID: 15638767]
  3. J Hosp Infect. 2007 Oct;67(2):135-41 [PMID: 17884248]
  4. Curr Eye Res. 2005 May;30(5):385-94 [PMID: 16020269]
  5. Mol Cell. 2002 Nov;10(5):1033-43 [PMID: 12453412]
  6. Blood. 1997 Oct 1;90(7):2796-803 [PMID: 9326247]
  7. Infect Immun. 1995 Apr;63(4):1291-7 [PMID: 7890387]
  8. Biochim Biophys Acta. 2006 Sep;1758(9):1408-25 [PMID: 16716248]
  9. Science. 2006 Mar 24;311(5768):1770-3 [PMID: 16497887]
  10. Pediatr Res. 1987 Feb;21(2):205-10 [PMID: 3029658]
  11. Immunology. 2002 May;106(1):20-6 [PMID: 11972628]
  12. Blood. 2003 Apr 15;101(8):3265-73 [PMID: 12515729]
  13. Blood. 2003 May 1;101(9):3460-8 [PMID: 12522000]
  14. Pediatrics. 1977 Oct;60(4):467-72 [PMID: 905012]
  15. Infect Immun. 2000 Jul;68(7):4297-302 [PMID: 10858248]
  16. J Obstet Gynaecol Res. 2005 Aug;31(4):314-22 [PMID: 16018778]
  17. Ann Otol Rhinol Laryngol. 2007 Aug;116(8):599-603 [PMID: 17847728]
  18. J Biol Chem. 1997 Jun 13;272(24):15258-63 [PMID: 9182550]
  19. Curr Opin Hematol. 2001 Jan;8(1):23-7 [PMID: 11138622]
  20. Biochem Biophys Res Commun. 2002 May 24;293(5):1314-8 [PMID: 12054656]
  21. N Engl J Med. 2002 Oct 10;347(15):1199-200 [PMID: 12374882]
  22. Acta Paediatr. 2004 Jun;93(6):786-90 [PMID: 15244228]
  23. Blood. 1994 Feb 1;83(3):799-807 [PMID: 8298140]
  24. Pediatr Res. 1984 Nov;18(11):1148-53 [PMID: 6096799]
  25. Pediatrics. 1999 Dec;104(6):1327-33 [PMID: 10585984]
  26. J Immunol. 2004 Jan 15;172(2):1146-56 [PMID: 14707090]
  27. Infect Immun. 1999 May;67(5):2561-6 [PMID: 10225921]
  28. Proc Natl Acad Sci U S A. 1995 Jan 3;92(1):195-9 [PMID: 7529412]
  29. Blood. 2001 May 1;97(9):2561-7 [PMID: 11313242]
  30. J Immunol. 2007 Aug 15;179(4):2060-3 [PMID: 17675463]
  31. J Exp Med. 2000 Oct 2;192(7):1069-74 [PMID: 11015447]
  32. J Exp Med. 1999 Jun 7;189(11):1847-52 [PMID: 10359588]
  33. Pediatr Res. 1986 Apr;20(4):296-300 [PMID: 3703618]
  34. FASEB J. 2005 Jul;19(9):1067-77 [PMID: 15985530]
  35. Curr HIV Res. 2007 Jul;5(4):410-5 [PMID: 17627504]
  36. J Biol Chem. 1995 Jan 20;270(3):1350-61 [PMID: 7836402]
  37. Pediatrics. 1996 Sep;98(3 Pt 1):357-61 [PMID: 8784356]
  38. Blood. 2000 Nov 1;96(9):3086-93 [PMID: 11049988]
  39. Nat Rev Microbiol. 2005 Mar;3(3):238-50 [PMID: 15703760]
  40. Blood. 2001 Jun 15;97(12):3951-9 [PMID: 11389039]
  41. Blood. 1997 May 15;89(10):3503-21 [PMID: 9160655]
  42. Curr Drug Targets Infect Disord. 2002 Mar;2(1):79-83 [PMID: 12462155]
  43. Int J Hematol. 2007 May;85(4):304-11 [PMID: 17483073]
  44. FEBS Lett. 1995 Oct 23;374(1):1-5 [PMID: 7589491]
  45. Gut. 1996 Mar;38(3):414-20 [PMID: 8675096]
  46. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):552-7 [PMID: 17368184]
  47. J Immunol. 2006 Mar 1;176(5):3044-52 [PMID: 16493063]
  48. J Biol Chem. 1993 May 15;268(14):10425-32 [PMID: 7683678]
  49. J Biol Chem. 1999 Aug 6;274(32):22445-51 [PMID: 10428818]
  50. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9541-6 [PMID: 9689116]

MeSH Term

Acute-Phase Proteins
Adult
Antimicrobial Cationic Peptides
Cathelicidins
Cholecalciferol
Female
Flow Cytometry
Humans
Immunity, Innate
Infant, Newborn
Lipocalin-2
Lipocalins
Male
Monocytes
Neutrophils
Proto-Oncogene Proteins
Rickets
Treatment Outcome
Young Adult

Chemicals

Acute-Phase Proteins
Antimicrobial Cationic Peptides
Cathelicidins
LCN2 protein, human
Lipocalin-2
Lipocalins
Proto-Oncogene Proteins
Cholecalciferol

Word Cloud

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