CD36 belongs to scavenger receptor class B and is a fatty acid translocase. Our previous studies have suggested that the receptor may be involved in regulation of responses to endotoxin and inflammation of the lungs in mice. In current studies, we have designed a group of helical peptides that interact with and modulate the activities of CD36 and tested their activities against endothelial barrier dysfunction and acute lung injuries in mice. Peptides that inhibit CD36 activities including L37pA, ELR-B and ELR-BP reversed or mitigated the barrier disruptive activities induced by LPS, HKSA, truncated phospholipids and histone H3 as measured by TER (trans-endothelial electric resistance). In consistence with this, the peptides also enhanced the barrier protective activities of OxPAPC. The peptides were delivered intravenously to mice treated with LPS or HKSA to induce acute lung injuries. It has been observed that among peptides that antagonize the activities of CD36, L37pA, ELR-B and ELR-BP have demonstrated inhibitory effects on acute lung injuries induced by LPS characterized by reduced extravagance of inflammatory cells from circulation to bronchoalveolar lavage (BAL) and a decrease in protein concentration in BAL fluid from the peptide-treated mice. The observation indicates that modulation of CD36 activities by peptide inhibitors is a novel strategy to reduce acute lung injuries induced by pro-inflammatory agents.
