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.
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Abbreviations
- fMLP:
-
formyl-methionine-leucine-phenylalanine
- ITIM:
-
immunoreceptor tyrosine-based inhibitory motif
- MFI:
-
mean fluorescence intensity
- rhGM-CSF:
-
recombinant human granulocyte-macrophage colony-stimulating factor
- SHP-1:
-
Src homology domain 2-containing tyrosine phosphatase-1
- Siglec:
-
Sialic acid-binding immunoglobulin-like lectin
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Acknowledgements
We thank the obstetricians and the Labor & Delivery staff at SSM St. Mary's Health Center and particularly the adult blood donors for helping us obtain samples critical for our studies.
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Supported by Grant HD47401 from NIH/NICHD (to J.M.K), the Fleur-de-Lis Foundation (to R.R.), and the Pediatric Research Institute, Department of Pediatrics, Saint Louis University (to J.M.K.).
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Rashmi, R., Bode, B., Panesar, N. et al. Siglec-9 and SHP-1 Are Differentially Expressed in Neonatal and Adult Neutrophils. Pediatr Res 66, 266–271 (2009). https://doi.org/10.1203/PDR.0b013e3181b1bc19
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DOI: https://doi.org/10.1203/PDR.0b013e3181b1bc19
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