TY  - JOUR
AU  - Bozinovski, S
AU  - Cross, M
AU  - Vlahos, R
AU  - Jones, JE
AU  - Hsuu, K
AU  - Tessier, PA
AU  - Reynolds, EC
AU  - Hume, DA
AU  - Hamilton, JA
AU  - Geczy, CL
AU  - Anderson, GP
Y2  - 2014/05/21
Y1  - 2005/01/01
SN  - 1535-3893
UR  - http://hdl.handle.net/11343/26124
AB  - Neutrophilic lung inflammation is an essential component of host defense against diverse eukaryotic and prokaryotic pathogens, but in chronic inflammatory lung diseases, such as chronic obstructive lung disease (COPD), severe asthma, cystic fibrosis, and bronchiolitis, it may damage the host. Glucocorticosteroids are widely used in these conditions and in their infectious exacerbations; however, the clinical efficacy of steroids is disputed. In this study, we used a proteomic approach to identify molecules contributing to neutrophilic inflammation induced by transnasal administration of lipopolysaccharide (LPS) that were also resistant to the potent glucocorticosteroid dexamethasone (Dex). We confirmed that Dex was biologically active at both the transcript (suppression of GM-CSF and TNFalphatranscripts) and protein levels (induction of lipocortin) and used 2D-PAGE/MALDI-TOF to generate global expression profiles, identifying six LPS-induced proteins that were Dex resistant. Of these, S100A8, a candidate neutrophil chemotactic factor, was profiled in detail. Steroid refractory S100A8 expression was highly abundant, transcriptionally regulated, secreted into lung lavage fluid and immunohistochemically localized to tissue infiltrating neutrophils. However, in marked contrast to other vascular beds, neutralizing antibodies to S100A8 had only a weak anti-neutrophil recruitment effect and antibodies against the related S100A9 were ineffective. These data highlight the need for extensive in vivo profiling of proteomically identified candidate molecules and demonstrates that S100A8, despite its abundance, resistance to steroids and known chemotactic activity, is unlikely to be an important determinant of LPS-induced neutrophilic lung inflammation in vivo.
LA  - English
PB  - AMER CHEMICAL SOC
KW  - Medical Biochemistry: Proteins and Peptides; Endocrine Organs and Diseases (incl. Diabetes)
T1  - S100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo
DO  - 10.1021/pr049829t
IS  - JOURNAL OF PROTEOME RESEARCH
VL  - 4
IS  - 1
SP  - 136-145
L1  - /bitstream/handle/11343/26124/115886_4923.pdf?sequence=1&isAllowed=n
ER  -