Abstract 19: Fibrinogen Gamma-Chain Peptide-Coated, Adenosine Diphosphate-Encapsulated Liposomes Rescue Lethal Blast Lung Injury Hemorrhage via Purinergic Signaling

Background: Fibrinogen gamma-chain (HHLGGAKQAGDV, H12)-coated, adenosine-diphosphate (ADP)-encapsulated liposomes [H12-(ADP)-liposomes] that accumulate at bleeding sites via interaction with activated platelets via GPIIb/IIIa and release ADP. Objective: To elucidate the effect of H12-ADP-liposomes and its mechanisms on the lethal pulmonary hemorrhage following blast injury. Methods: Mice were pretreated with H12-ADP-liposomes (n=14), ADP-liposomes (n=10), PBS-liposomes (n=10) or normal saline (n=14). A single shot of laser induced shock wave (LISW, 1.8 J/cm2) caused lethal diffuse alveolar hemorrhage in mice. Furthermore, to examine the adenosine effect of H12-ADP-liposomes, adenosine A2A receptor antagonist (ZM241385, n=6) or adenosine A2B receptor antagonist (PSB 1115, n=6) was administered 1 hr before the H12-ADP-liposomes + LISW procedures. Among them, the acute prognosis (survival rates) and pathological injury score (blending area) were compared. The levels of albumin and MIP-2 in the bronchoalveloral lavage fluid (BALF) were measured after LISW in each group. Results: H12-ADP-liposomes significantly improved mouse survival (Figure) and reduced the pathological injury score than normal saline (35 vs 40, p=0.004, n=5). H12-ADP-liposomes reduced the albumin leakage (0.8 vs 1.3 mg/ml, p=0.03, n=6) and MIP-2 levels in the BALF (74 vs 355 pg/ml, p<0.01, n=6) than normal saline. Adenosine receptor (especially A2B) antagonists prevented from rescuing and reducing the BALF albumin and MIP-2 leakage by the H12-ADP-liposomes treatment. Conclusions: H12-ADP-liposomes may be effective for acute blast lung injury, functioning hemostasis and organ protection via anti-inflammatory purinergic signaling.