Developmental changes in circulating IL-8/CXCL8 isoforms in neonates.
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.
Maheshwari
Akhil
A
Department of Pediatrics, University of Alabama, Birmingham, AL 35294, USA. akhil@peds.uab.edu
Voitenok
Nikolai N
NN
Akalovich
Svetlana
S
Shaik
Sadiq S
SS
Randolph
David A
DA
Sims
Brian
B
Patel
Rakesh P
RP
Killingsworth
Cheryl R
CR
Fallon
Michael B
MB
Ohls
Robin K
RK
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D018925:Chemokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation; D016209:Interleukin-8 / Q000737:chemistry* / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D020033:Protein Isoforms; D013552:Swine
D018925:Chemokines; D016209:Interleukin-8; D020033:Protein Isoforms