Lysophosphatidic acid mitigates vascular permeability and allergic rhinitis in mice.

Abstract

Background: The pathophysiology of allergic rhinitis involves vasodilation and increased vascular permeability. Current treatments primarily target inflammatory mediators, with a limited focus on vascular abnormalities. We aimed to investigate whether lysophosphatidic acid (LPA), which regulates vascular stability through its receptor, LPAR4, could ameliorate allergic symptoms by normalizing vascular function.

Methods: A mouse model of ragweed-induced allergic rhinitis was treated with LPA. We assessed the sneezing frequency, serum immunoglobulin E (IgE) levels, eosinophil infiltration, vascular permeability, and vessel morphology. In vitro studies were performed to examine the protective effects of LPA on histamine-induced endothelial barrier disruption. Transcriptome analysis of nasal vascular endothelial cells was performed to identify the underlying molecular mechanisms.

Results: LPA administration significantly reduced the frequency of sneezing and eosinophil infiltration without affecting serum IgE levels. The Evans blue extravasation assay demonstrated that LPA treatment significantly reduced vascular permeability in the nasal tissue, while immunofluorescence analysis of nasal blood vessels showed normalization of vessel diameter. In vitro, LPA pre-treatment significantly protected against histamine-induced endothelial gap formation. Transcriptome analysis revealed that LPA normalized the expression of genes involved in interleukin (IL)-4/IL-13 signaling, platelet activation, and cell junction organization pathways.

Conclusions: LPA signaling uniquely addresses both vascular permeability and vasodilation in allergic rhinitis and represents a novel therapeutic approach that targets vascular abnormalities rather than immune responses. The ability of LPA to simultaneously normalize multiple vascular parameters suggests its potential as a complementary treatment for allergic diseases.