Developmental changes in circulating IL-8/CXCL8 isoforms in neonates

Akhil Maheshwari, Nikolai N. Voitenok, Svetlana Akalovich, Sadiq S. Shaik, David A. Randolph, Brian Sims, Rakesh P. Patel, Cheryl R. Killingsworth, Michael B. Fallon, Robin K. Ohls

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Interleukin-8 (IL-8/CXCL8) is widely expressed in fetal tissues although inflammatory changes are not seen. Circulating IL-8 is comprised of an endothelial-derived [ala-IL-8]77 isoform and another, more potent [ser-IL-8]72 secreted by most other cells; [ala-IL-8]77 can be converted into [ser-IL-8]72 by proteolytic removal of an N-terminal pentapeptide from [ala-IL-8]77. In this study, we show [ala-IL-8]77 is the predominant circulating isoform of IL-8 in premature neonates but not in term neonates/adults, who have [ser-IL-8]72 as the major isoform. This isoform switch from the less potent [ala-IL-8]77 to [ser-IL-8]72 correlates with a maturational increase in the neutrophil chemotactic potency of plasma IL-8. The emergence of [ser-IL-8]72 as the major isoform is likely due to increased plasma [ala-IL-8]77-convertase activity and/or changes in the cellular sources of IL-8. Developmental changes in IL-8 isoforms may serve to minimize its inflammatory effects in the fetus and also provide a mechanism to restore its full activity after birth.

Original languageEnglish (US)
Pages (from-to)12-16
Number of pages5
JournalCytokine
Volume46
Issue number1
DOIs
StatePublished - Apr 2009
Externally publishedYes

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Keywords

  • Chemokines
  • Interleukin-8
  • Isoforms
  • Neonate
  • Neutrophil

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

Cite this

Maheshwari, A., Voitenok, N. N., Akalovich, S., Shaik, S. S., Randolph, D. A., Sims, B., Patel, R. P., Killingsworth, C. R., Fallon, M. B., & Ohls, R. K. (2009). Developmental changes in circulating IL-8/CXCL8 isoforms in neonates. Cytokine, 46(1), 12-16. https://doi.org/10.1016/j.cyto.2008.12.022