S100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo

摘要: Neutrophilic lung inflammation is an essential component of host defense against diverse eukaryotic and prokaryotic pathogens, but in chronic inflammatory diseases, such as obstructive disease (COPD), severe asthma, cystic fibrosis, bronchiolitis, it may damage the host. Glucocorticosteroids are widely used these conditions their infectious exacerbations; however, clinical efficacy steroids disputed. In this study, we a proteomic approach to identify molecules contributing neutrophilic induced by transnasal administration lipopolysaccharide (LPS) that were also resistant potent glucocorticosteroid dexamethasone (Dex). We confirmed Dex was biologically active at both transcript (suppression GM-CSF TNFalphatranscripts) protein levels (induction lipocortin) 2D-PAGE/MALDI-TOF generate global expression profiles, identifying six LPS-induced proteins resistant. Of these, S100A8, candidate neutrophil chemotactic factor, profiled detail. Steroid refractory S100A8 highly abundant, transcriptionally regulated, secreted into lavage fluid immunohistochemically localized tissue infiltrating neutrophils. However, marked contrast other vascular beds, neutralizing antibodies had only weak anti-neutrophil recruitment effect related S100A9 ineffective. These data highlight need for extensive vivo profiling proteomically identified demonstrates despite its abundance, resistance known activity, unlikely be important determinant vivo.