Increased Leukocyte Phospholipase A₂Activity and Plasma Lysophosphatidylcholine Levels in Asthma and Rhinitis and Their Relationship to Airway Sensitivity to Histamine

Abstract

This study was carried out to determine leukocyte phospholipase A2 (PLA2) activity and plasma lysophosphatidylcholine (LPC) levels in normal subjects and in patients with asthma and rhinitis and to examine their relationship to airway sensitivity to histamine. Leukocyte PLA2 activity and plasma LPC levels were highly correlated (rs = 0.90), and were found significantly raised in both the disease groups, more so in the asthmatics. Both PLA2 activity and LPC levels showed overall negative correlations with the log dose of histamine producing a 35% fall in specific airway conductance (PD35 histamine) when the patients and the normal subjects were examined together (rs = -0.77 and rs = -0.83, respectively). The patients with leukocyte PLA2 activity more than 1.8 U (nmol 14C-AA released/mg protein/10 min at 30 degrees C) or plasma LPC levels more than 8.7% of total phospholipids (mostly asthmatics) showed high airway sensitivity to histamine (PD35 histamine less than or equal to 1 mg/ml). On the other hand, the PD35 histamine values of patients with leukocyte PLA2 activity equal to or less than 1.96 U or plasma LPC levels equal to or less than 8.7% overlapped with those of normal subjects in the range of 1.2 to 10 mg/ml. Lowering of plasma LPC levels, which probably reflect tracheobronchial LPC content as shown in guinea pigs, seems to be an essential step in the return of airway reactivity toward normal.

Increased levels of protein kinase C in lymphocytes in asthma: possible mechanism of regulation

“…PKC may also be activated by lysophosphatidylcholine (LPC) and other cis-unsaturated fatty acids produced by the action of phospholipase A 2 on phosphatidylcholine or DAG [15]. Increased activity of PLA 2 and LPC levels has been reported in lymphocytes of asthmatic patients [19], which may potentiate PKC activity, as observed in this investigation. Production of DAG and arachidonic acid have also been reported in lymphocytes of asthmatic patients [20].…”

Inflammation-associated lysophospholipids as ligands for CD1d-restricted T cells in human cancer

“…It is a major constituent of oxidized low density lipoprotein in atherosclerotic plaques, and elevated levels of lysophospholipids have been observed in allergic and autoimmune inflammation, asthma, and human cancer, including in MM. 25,26,30,31 Therefore, the findings made in this study may apply to the putative role for CD1d-restricted T cells in diverse inflammatory states. Staining human T cells with LPC-loaded CD1d dimers was inhibited in the presence of PC.…”

Anti‐inflammatory, membrane‐stabilizing interactions of salmeterol with human neutrophils in vitro

“…These membrane-stabilizing, anti-inflammatory properties of salmeterol are unlikely to be restricted to neutrophils since PAF and LPC, both of which are thought to play key roles in the pathogenesis of bronchial asthma and rhinitis (Barnes, 1989;Mehta et al, 1990;Zimmerman et al, 1990), are potent mediators of other inflammatory and cytotoxic processes. Apart from its pro-oxidative and cytotoxic properties, which are shared by PAF and LPAF, LPC also induces mast cell secretion by promoting influx of extracellular calcium (Marquardt & Walker, 1991), while exposure of respiratory epithelium to lysophospholipids and PAF is accompanied by ciliary dysfunction, cytotoxicity and impaired mucociliary clearance (Ganbo et al, 1991;Nieminen et al, 1991;Feldman et al, 1995).…”