Lentiviral vector-mediated delivery of lysophosphatidylcholine acyltransferase 1 attenuates airway inflammation in ovalbumin-induced allergic asthmatic mice.

BACKGROUND

Lysophosphatidylcholine (LPC) is generated through the hydrolysis of phospha-tidylcholine (PC) by phospholipase A2 and is converted back to PC by lysophosphatidylcholine acyltransferase 1 (LPCAT1). Elevated levels of (LPC) are known to play a pathogenic role in the inflammatory injury of asthma. However, the role of LPCAT1 in asthma has not yet been reported.

OBJECTIVE

To determine whether the exogenous expression of LPCAT1, delivered by using a recombinant lentiviral vector, could attenuate airway inflammation in asthmatic mice.

METHODS

Recombinant lentivirus carrying cDNA encoding LPCAT1 (Lenti-LPCAT1), or EGFP (Lenti-EGFP) as a control, was constructed. BALB/c mice were sensitised with ovalbumin (OVA), and intratracheally pre-treated with an endobronchial administration of the recombinant lentivirus intratracheally 72 hours before the first challenge. After the last OVA challenges, the mice were assessed for airway inflammation, airway hyper-responsiveness and lipid levels.

RESULTS

Lenti-LPCAT1-infected HEK293T cells expressed exogenous recombinant LPCAT1 protein that showed high activity of the LPC acyltransferase. OVA sensitisation and challenge significantly increased the levels of saturated species LPC 16:0 and LPC 18:0 levels in the bronchoalveolar lavage fluid (BALF) compared with wild-type mice respectively. The intratracheal Lenti-LPCAT1 instillation obviously down-regulated the OVA-induced release of LPC 16:0 and LPC 18:0. Treatment with Lenti-LPCAT1 ameliorated OVA-induced airway hyper-responsiveness and reduced airway eosinophilia infiltration in lung tissue. Furthermore, the secretion of eotaxin and Th2-associated cytokines IL-5 and IL-13 were inhibited in BALF. The level of OVA-specific IgE in serum was suppressed.

CONCLUSIONS

These results suggested that the exogenous expression of LPCAT1 may attenuate eosinophil inflammation in the airway by down-regulating the LPC 16:0 and LPC 18:0 BALF levels in asthmatic mice.