Dysregulation of lipidomic profile and antiviral immunity in response to hyaluronan in patients with severe asthma

Hyaluronan (HA), a major component of extracellular matrix, accumulates in the lung and serum of asthmatic patients and correlates with disease severity.3 Low-molecular-weight (LMW) forms of HA generated during tissue injury or inflammation have been linked to asthma,3,4 but the mechanisms of that link are not well understood. Recently, we described the mechanism by which LMW HA can activate cytosolic phospholipase A2α (cPLA2α) and arachidonic acid (AA) production.5 Previously, we reported increased expression of cPLA2α in PBMCs of patients with severe asthma.6 cPLA2α is a rate-limiting enzyme in eicosanoid production, which is responsible for liberation of AA from cellular membranes.5 AA is the precursor of leukotrienes, prostaglandins (PGs), hydroxyeicosatetranoic acids (HETEs), thromboxanes, lipoxins, and epoxides, many of which are involved in asthma pathogenesis,7 and they are altered in patients with viral infections.8 A thorough analysis of LMW HA's effects on the lipidomic profile or global gene expression in asthmatic patients has never been performed, and its possible influence on the disease progression has not been noted. [...]we performed a systemic analysis of LMW HA signaling in PBMCs of patients with mild-to-moderate and severe asthma by using liquid chromatography and mass spectrometry combined with microarray, real-time PCR, and multiplex protein analyses. Thirteen asthmatic patients and six control subjects were enrolled under a National Heart, Lung, and Blood Institute review board-approved protocol (99-H-0076). Supplementary data References 1 N.N. Jarjour, S.C. Erzurum, E.R. Bleecker, W.J. Calhoun, M. Castro, S.A. Comhair, Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe...