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

Renata Ximenes Lins1, Maria Cristina de Assis, Carolina Diettrich Mallet de Lima

  • 1Departamento de Microbiologia, Imunologia e Parasitologia - FCM/UERJ, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87 fundos, 3 degrees andar. 20 551-030, Rio de Janeiro, RJ, Brazil.

Microbes and Infection
|November 26, 2009
PubMed

Insights

Pseudomonas aeruginosa cytotoxin ExoU alters ICAM-1 expression by cleaving membrane-bound ICAM-1 into soluble ICAM-1. This process involves phospholipase A2 activity and the cyclooxygenase pathway, impacting leukocyte recruitment.

Area of Science:

  • Microbiology
  • Immunology
  • Cell Biology

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen.
  • ExoU is a cytotoxin secreted by P. aeruginosa.
  • ExoU has phospholipase A2 (PLA2) activity and pro-inflammatory properties.

Purpose of the Study:

  • To investigate if ExoU modulates adhesion molecule expression in host cells.
  • To determine ExoU's role in leukocyte recruitment to infected tissues.

Main Methods:

  • Infection of endothelial cells with ExoU-producing and non-producing P. aeruginosa strains.
  • Analysis of membrane-bound ICAM-1 (mICAM-1) and soluble ICAM-1 (sICAM-1) levels.
  • Investigation of the involvement of ExoU's PLA2 activity and the cyclooxygenase (COX) pathway.

Main Results:

  • ExoU down-regulated mICAM-1 and up-regulated sICAM-1 release from infected endothelial cells.
  • ICAM-1 modulation was dependent on ExoU's PLA2 activity and the COX pathway.
  • No changes in ICAM-1 mRNA levels were observed, suggesting proteolytic cleavage.

Conclusions:

  • ExoU proteolytically cleaves mICAM-1 to produce sICAM-1.
  • This cleavage is mediated by ExoU's PLA2 activity via a COX-dependent pathway.
  • ExoU's modulation of ICAM-1 may contribute to leukocyte recruitment in P. aeruginosa infections.

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