Siglec-9 and SHP-1 are differentially expressed in neonatal and adult neutrophils.

Abstract:

:Neonatal PMN (polymorphonuclear neutrophils) exhibit altered inflammatory responsiveness and greater longevity compared with adult PMN; however, the involved mechanisms are incompletely defined. Receptors containing immunoreceptor tyrosine-based inhibitory motif (ITIM) domains promote apoptosis by activating inhibitory phosphatases, such as Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1), that block survival signals. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9, an immune inhibitory receptor with an ITIM domain, has been shown to induce cell death in adult PMN in association with SHP-1. To test our hypothesis that neonatal PMN inflammatory function may be modulated by unique Siglec-9 and SHP-1 interactions, we compared expression of these proteins in adult and neonatal PMN. Neonatal PMN exhibited diminished cellular expression of Siglec-9, which was phosphorylated in the basal state. Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment decreased Siglec-9 phosphorylation levels in neonatal PMN but promoted its phosphorylation in adult PMN, observations associated with altered survival signaling. Although SHP-1 expression was also diminished in neonatal PMN, GM-CSF treatment had minimal effect on phosphorylation status. Further analysis revealed that Siglec-9 and SHP-1 physically interact, as has been observed in other immune cells. Our data suggest that age-specific interactions between Siglec-9 and SHP-1 may influence the altered inflammatory responsiveness and longevity of neonatal PMN.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Rashmi R,Bode BP,Panesar N,King SB,Rudloff JR,Gartner MR,Koenig JM

doi

10.1203/PDR.0b013e3181b1bc19

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

266-71

issue

3

eissn

0031-3998

issn

1530-0447

journal_volume

66

pub_type

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