FLA-PA, a ~52 kDa protein, is flagellin isolated from P. aeruginosa, a virulent Gram negative bacterial pathogen. This bacterium is implicated in respiratory tract infections, particularily in cystic fibrosis patients.
Flagellin from P. aeruginosa is extracted by acid hydrolysis and is purified by ultrafiltration and chromatography.
Flagellin is a proinflammatory molecule recognized by distinct types of pattern recognition receptors (PRRs); the surface localized Toll-like receptor (TLR5)  and the cytosolic NOD-like receptors (NLRs), NLRC4 and NAIP5 .
Extracellular flagellin is detected by TLR5 resulting in MyD88-mediated NF-κB activation, cytokine and nitric oxide production depending on the nature of the TLR5 signaling complex .
Intracellular flagellin is detected by NLRC4 (also known as IPAF) and NAIP5. Recognition by NLRC4 and NAIP5, leads to inflammasome assembly, triggering caspase-1 activation of IL-1β and IL-18.
- Hayashi F. et al., 2001. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410(6832):1099-103.
- Zhao et al., 2011. The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature. 2011 Sep 14;477(7366):596-600.
- Mizel SB. et al., 2003. Induction of macrophage nitric oxide production by Gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4 complexes. J Immunol. 170(12):6217-23.