https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48016 To the Editor: The major 17q12-21 asthma susceptibility and exacerbation locus1 has been identified as the only genetic locus that is also reproducibly associated with total white blood cell count.2 However, it is not known whether there is a common gene within this locus that links these phenotypic traits. The colony-stimulating factor-3 (CSF3) gene, alternatively known as G-CSF, resides within this locus. CSF3 binds exclusively to CSF3 receptor (CSF3R, or CD114/G-CSFR), which is highly expressed on mature neutrophils and to a lesser extent on mononuclear cells, platelets, and lung interstitial stromal cells. Although CSF3R/CD114 signaling can dictate the intensity of the host defense inflammatory response during bacterial infection by regulating neutrophil granulopoiesis and trafficking, its role in the infection-dependent transition to persistent, severe asthma has not been investigated. Neonatal colonization of the nasopharynx by potentially pathogenic bacteria including Streptococcus pneumoniae is also a risk factor for asthma development.3 The Childhood Asthma Study found that children with atopy and chronic wheeze at age 5 years were twice as likely to have been colonized with S pneumoniae as neonates.4 The authors suggest that transient incursions of nasopharyngeal bacteria into the lower airways triggered by a fever-causing viral respiratory infection (respiratory syncytial virus or influenza virus) increases the risk of developing persistent asthma in atopic children. However, a plausible mechanism linking these cofactors is yet to be identified. In this study, we tested the hypothesis that CSF3-CSF3R signaling dictates the severity of infectiondependent asthma at a cellular and molecular level.]]> Wed 15 Feb 2023 10:19:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34211 Thu 09 Dec 2021 11:02:18 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23760 4 (LXA,sub>4) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA₂ 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA₄. Human lung macrophages (CD68⁺) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC₅₀ 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA₄ but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.]]> Sat 24 Mar 2018 07:11:08 AEDT ]]>