Pathophysiological changes of gram-negative bacterial infection can be reproduced by a synthetic peptide mimicking loop L7 sequence of Haemophilus influenzae porin.
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.
Vitiello
Mariateresa
M
Department of Experimental Medicine-II University of Naples, Via De Crecchio 7, 80138 Naples, Italy.
Galdiero
Stefania
S
D'Isanto
Marina
M
D'Amico
Michele
M
Di Filippo
Clara
C
Cantisani
Marco
M
Galdiero
Marilena
M
Pedone
Carlo
C
D020816:Amino Acid Motifs; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D005342:Fibrinolysis; D016905:Gram-Negative Bacterial Infections / Q000378:metabolism / Q000503:physiopathology*; D006193:Haemophilus influenzae / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D018272:Porins / Q000008:administration & dosage* / Q000138:chemical synthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D001426:Bacterial Proteins; D010455:Peptides; D018272:Porins