SCD14 in Bronchoalveolar Lavage 18, 42 and 162 Hours After Segmental Allergen Provocation

Abstract

Lipopolysaccharides (LPS) have been associated with a protective role in the development of asthma while higher levels of endotoxin have been linked with more severe asthma. LPS recruit neutrophils and eosinophils and activate macrophages via the CD14 receptor. The soluble CD 14 receptor (sCD14) has been found in bronchoalveolar lavage fluid in different diseases including allergic asthma. To elucidate the kinetics and the regulation of sCD14 concentrations in BAL in asthma, 18 patients with allergic asthma underwent segmental allergen challenge at different time points (10 min, 18, 42 and 162 h). In addition, CD14(+) peripheral blood mononuclear cell (PBMC-CD14(+)) cultures from seven allergic and seven non-allergic subjects were stimulated with LPS, leukotrien D(4) (LTD(4)), a combination of LPS and LTD(4), IL-17 and LTD(4) in presence of the leukotriene-receptor antagonist (LTRA) Montelukast for 6, 12 and 24 h. sCD14 concentrations in BAL and the supernatants were measured by ELISA. sCD14 concentrations in BAL were significantly increased 18 h after allergen challenge and peaked at 42 h. At 162 h, concentrations had returned to baseline levels. In PBMC-CD14(+) cultures, sCD14 levels increased significantly 24 h after stimulation with LTD(4) and Montelukast was able to block LTD(4)-induced stimulation. Allergen challenge leads to a significant increase in sCD14 concentrations in BAL and might modulate the allergen-induced inflammation. In addition, LTD(4) might play a role in the release of sCD14, and it could be speculated that sCD14 reduction by LTRA might contribute to the mechanisms of LTRA in the treatment of allergic asthma.