Post-treatment with H12-(ADP)-liposomes after LPS challenge ameliorated coagulopathy and critical organ injury in rats.

Abstract

Background: Liposomes coated with fibrinogen γ-chain (HHLGGAKQAGDV, H12) peptide and encapsulating adenosine-diphosphate (ADP) [H12-(ADP)-liposomes] can augment platelet aggregation via glycoprotein IIb/IIIa receptors displayed on activated platelets. H12-(ADP)-liposomes release ADP, which is metabolized into adenosine that has tissue-protective effects. This study evaluated the life-saving efficacy of post-treatment with H12-(ADP)-liposomes in rats with LPS-induced coagulopathy and critical organ injuries.

Methods: LPS (10 mg/kg) was administered intraperitoneally to rats. The rats were then treated with an intravenous injection of either H12-(ADP)-liposomes or normal saline (vehicle control) 4 h later.

Results: Post-treatment with H12-(ADP)-liposomes significantly shortened the coagulation time compared to the vehicle treatment at 8 h after LPS challenge and reduced expression of CD62P, a marker of platelet activation, on CD61⁺ platelets at 12 h. H12-(ADP)-liposome post-treatment also normalized the elevated levels of neutrophil elastase (complex) at 6-24 h and citrullinated histone H3 in bronchoalveolar lavage fluid at 24 h. H12-(ADP)-liposome-treated rats showed reductions in the pathological injury score for the lungs and kidneys at 8 h. The survival rates of rats given H12-(ADP)-liposomes were markedly improved 24 h after LPS challenge relative to vehicle-treated rats (50% vs. 21%, p = 0.038).

Conclusions: These findings suggest that post-treatment with H12-(ADP)-liposomes ameliorates LPS-induced coagulopathy and neutrophil activation, thereby improving critical organ injuries and survival in LPS-challenged rats.