Phospholipase A2 and arachidonate increase in bronchoalveolar lavage fluid after inhaled antigen challenge in asthmatics.

Abstract

Phospholipases A2 (PLA2) hydrolyze phospholipids resulting in the release of fatty acids including arachidonic acid (AA) and lysophospholipids. AA, in turn, serves as a substrate for the synthesis of leukotrienes which can cause bronchoconstriction and airways edema and appear to be important mediators of clinical asthma. Further, lysophospholipids may be cytotoxic and/or impair the function of surfactant. We examined the release of secretory PLA2 (sPLA2) and AA into the airways after antigen challenge in 16 subjects with allergic asthma. Asthmatic subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) before and after inhaled antigen challenge; in addition, a single BAL, without inhaled antigen, was performed in 10 control subjects. BAL was obtained at 4 h (n = 7), the time of the late asthmatic response (LAR) (n = 5), or 24 h (n = 4) after challenge. There was no difference between normal and asthmatic subjects in either BAL fluid (BALF) sPLA2 activity or AA concentration at baseline. Both sPLA2 and AA increased after antigen challenge (p < 0.01 and 0.05, respectively). These changes were most marked 4 h after challenge (p < 0.03 for both). sPLA2 may play an important role in the generation of AA in patients with asthma.

Enhancement of Mast Cell Survival: A Novel Function of Some Secretory Phospholipase A2 Isotypes

“…Thus, further studies are necessary to definitively identify the circulating sPLA 2 isotypes. We and others have shown that sPLA 2 isotypes are released after allergen challenge of asthmatic airways (82,83), and we postulate that these sPLA 2 isotypes have the capacity to influence the recruitment and function of cells that participate in airway disease. A study by Reddy and Herschman (84) showing that mast cells can provide sPLA 2 to fibroblasts for PG production supports this hypothesis.…”

Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase

“…This mechanism for LPA formation, which has been demonstrated after ␣ 2 -adrenoreceptor stimulation of adipocytes (254), may function in airway epithelial cells (199). Group II secretory PLAs have been detected in bronchoalveolar lavage from patients with the acute respiratory distress syndrome (ARDS) (5, 87), ovalbumin-sensitized guinea pigs (215), and antigen-challenged asthmatics (20,36). S1P can be generated by sphingosine kinase activity on the plasma membrane (142,177).…”

Secretory Phospholipases A2 Activate Selective Functions in Human Eosinophils

“…Increased levels of extracellular sPLA 2 s have been detected in the plasma of patients affected by systemic inflammatory diseases such as acute pancreatitis (4), septic shock (5), extensive burns (6), and autoimmune diseases (7). These molecules also accumulate in inflammatory fluids such as the synovial fluid of patients with rheumatoid arthritis (8 -10), the bronchoalveolar lavage of patients with bronchial asthma (11,12), and the nasal secretions of patients with allergic rhinitis (13,14). sPLA 2 s released in plasma or within inflamed tissues are enzymatically active molecules, and they participate in systemic or local inflammatory reactions by releasing AA from outer cell membrane phospholipids (2,15).…”