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Plasminogen activator inhibitor type I contributes to protective immunity during experimental Gram-negative sepsis

L M Kager1, W J Wiersinga, J J T H Roelofs

  • 1Center for Experimental and Molecular Medicine, Center for Infection and Immunity Amsterdam, Amsterdam, the Netherlands. l.m.kager@amc.uva.nl

Journal of Thrombosis and Haemostasis : JTH
|August 19, 2011
PubMed
Abstract

Insights

Plasminogen activator inhibitor type 1 (PAI-1) protects against severe Burkholderia pseudomallei sepsis. PAI-1 deficiency increases mortality, bacterial load, inflammation, and organ injury in melioidosis models.

Area of Science:

  • Infectious Diseases
  • Immunology
  • Microbiology

Background:

  • Melioidosis, caused by Burkholderia pseudomallei, is a significant cause of sepsis in Southeast Asia.
  • Elevated levels of plasminogen activator inhibitor type 1 (PAI-1) are observed in melioidosis patients.

Purpose of the Study:

  • To investigate the protective role of PAI-1 in experimental melioidosis.
  • To understand PAI-1's influence on bacterial growth, inflammation, and coagulation during B. pseudomallei infection.

Main Methods:

  • Intranasal infection of wild-type and PAI-1-deficient mice with B. pseudomallei.
  • Assessment of bacterial loads, cytokine levels, coagulation parameters, organ injury markers, and survival rates.
  • Histopathological analysis of lung, liver, and kidney tissues.

Main Results:

  • PAI-1-deficient mice exhibited a 100% mortality rate compared to 58% in wild-type mice.
  • Increased bacterial loads, heightened proinflammatory cytokine levels, and enhanced coagulation activation were observed in PAI-1-deficient mice.
  • Significant hepatocellular injury and renal failure were noted in PAI-1-deficient animals.

Conclusions:

  • PAI-1 plays a crucial protective role in severe Gram-negative sepsis caused by B. pseudomallei.
  • PAI-1 limits bacterial proliferation, dampens inflammation, and mitigates coagulation abnormalities, thereby reducing distant organ damage.

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