Oxidized low-density lipoprotein activates migration and degranulation of human granulocytes.

Abstract

Oxidized low-density lipoprotein (oxLDL) has been reported as a major participant in the pathogenesis of atherosclerosis. We hypothesized that oxLDL can also interact with granulocytes during inflammatory airway diseases, such as asthma. To test the chemotactic effect of oxLDL, isolated human peripheral granulocytes were added to the upper chambers of Transwell filters and migration in response to oxLDL was determined. Cu+2-oxidized LDL stimulated neutrophil (23.4 +/- 3.2% for 100 microg/ml oxLDL versus 2.9 +/- 1.1% for buffer, P < 0.05) and eosinophil (19.3 +/- 3.5% versus 0.6 +/- 0.02% for buffer, P < 0.05) chemotaxis in a concentration-dependent manner. The magnitude of chemotaxis was dependent on the degree of LDL oxidation. Granulocyte transmigration across IL-1beta-activated human pulmonary microvascular endothelial cell monolayers was similarly stimulated by oxLDL. OxLDL activated significant degranulation of both neutrophils (100.9 +/- 9.8 versus 49.6 +/- 8.4 ng lactoferrin released/5 x 105 neutrophils for buffer, P < 0.05) and eosinophils (342 +/- 115.4 versus 85.8 +/- 30.4 ng eosinophil-derived neurotoxin/1 x 106 eosinophils for buffer, P < 0.05). Therefore, in vivo influx and oxidation of LDL may be an important mediator for the initiation of bronchial inflammation where granulocytes are recruited to the lung.