Pathophysiological changes of gram-negative bacterial infection can be reproduced by a synthetic peptide mimicking loop L7 sequence of Haemophilus influenzae porin.

Abstract

Several in vivo models have been used to dissect the molecular mechanisms that contribute to activate the coagulation and fibrinolytic systems by bacteria and bacterial products but many aspects remain poorly understood. In this study we examined the in vivo effect of the synthetic peptide corresponding to loop L7 from Haemophilus influenzae type b (Hib) porin to evaluate its role on the coagulative/fibrinolytic cascade and the circulating markers of endothelial injury. Plasma was obtained from rats injected intravenously with loop L7, Hib porin or a scrambled peptide and tested for fragment 1+2 (F1+2), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type I (PAI-1) antigen, von Willebrand factor (vWF) and soluble E-selectin (sE-selectin). The coagulative/fibrinolytic cascade was impaired as shown by PAI-1 level increased. Concomitantly, E-selectin, a marker of endothelial injury, was also significantly elevated. In addition either loop L7 or Hib porin injection induced hyperglycaemia and inflammatory cytokine production. The data were correlated with hemodynamic functions. The results indicate that loop L7 plays an essential role in the pathophysiologic events observed during gram-negative infection. These findings may have implications for the development of alternative therapies to counteract excessive inflammatory responses during septic shock.

• Authors: Mariateresa Vitiello, Stefania Galdiero, Marina D'Isanto, Michele D'Amico, Clara Di Filippo, Marco Cantisani, Marilena Galdiero, Carlo Pedone
• Journal: Microbes and infection (Microbes Infect) Vol. 10 Issue 6 Pg. 657-63 (May 2008) ISSN: 1286-4579 [Print] France
• PMID: 18462971 (Publication Type: Journal Article)

Chemical References

• Bacterial Proteins
• Peptides
• Porins

Topics

• Amino Acid Motifs
• Animals
• Bacterial Proteins (administration & dosage, chemistry, genetics)
• Disease Models, Animal
• Fibrinolysis
• Gram-Negative Bacterial Infections (metabolism, physiopathology)
• Haemophilus influenzae (chemistry)
• Peptides (administration & dosage, chemical synthesis, chemistry)
• Porins (administration & dosage, chemical synthesis)
• Rats
• Rats, Sprague-Dawley