ExoU modulates soluble and membrane-bound ICAM-1 in Pseudomonas aeruginosa-infected endothelial cells

• Published in: Microbes and infection 2010-02, Vol.12 (2), p.154-161
• Main Authors: Lins, Renata Ximenes, de Assis, Maria Cristina, Mallet de Lima, Carolina Diettrich, Freitas, Carla, Maciel Plotkowski, Maria Cristina, Saliba, Alessandra Mattos
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - metabolism; Bacteriology; Biological and medical sciences; Cell Line; Cyclooxygenase 2 - metabolism; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelial Cells - microbiology; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Endothelium, Vascular - microbiology; ExoU; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; ICAM-1; Inflammation; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Leukocidins - metabolism; Lipoxygenase - metabolism; Microbiology; Miscellaneous; Pseudomonas aeruginosa; Pseudomonas aeruginosa - metabolism; Pseudomonas aeruginosa - pathogenicity; Type III secretion system
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2009.11.005

ExoU, a Pseudomonas aeruginosa cytotoxin injected via the type III secretion system into host cells, possesses eicosanoid-mediated proinflammatory properties due to its phospholipase A 2 (PLA 2) activity. This report addressed the question whether ExoU may modulate the expression of adhesion molecules in host cells, therefore contributing to the recruitment of leukocyte into infected tissues. ExoU was shown to down-regulate membrane-bound ICAM-1 (mICAM-1) and up-regulate the release of soluble ICAM-1 (sICAM-1) from P. aeruginosa-infected endothelial cells. The modulation of ICAM-1 depended on the direct effect of the ExoU PLA 2 activity and involved the cyclooxygenase (COX) pathway. No differences in mICAM-1 and sICAM-1 mRNA levels were observed when cultures were infected with the ExoU-producing PA103 strain or the mutant PA103Δ exoU, suggesting that ExoU may proteolytically cleave mICAM-1, producing sICAM-1 in a COX-dependent pathway.