Published ahead of print on May 30, 2003, doi:10.1165/rcmb.2002-0257OC
© 2003 American Thoracic Society DOI: 10.1165/rcmb.2002-0257OC Oxidized Low-Density Lipoprotein Activates Migration and Degranulation of Human GranulocytesDepartment of Medicine, Allergy and Immunology Division, University of Wisconsin, Madison, Wisconsin; College of Medicine, Gyeongsang National University, Chinju, Korea; and Department of Allergic Disease Research, Mayo Clinic, Rochester, Minnesota Address correspondence to: Julie B. Sedgwick, Ph.D., University of Wisconsin, H6/355 CSC-3244 600 Highland Ave., Madison, WI 53792. E-mail: jxs{at}medicine.wisc.edu 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 µg/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-1ß–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.
Abbreviations: absorbance at 234 nm, Abs234 • cytochalasin B, CB • eosinophil-derived neurotoxin, EDN • ethylenediaminetetraacetate, EDTA • fluorescence activated cell sorting, FACS • fetal calf serum, FCS • granulocyte-macrophage colony-stimulating factor, GM-CSF • Hanks balanced salt solution, HBSS • human pulmonary microvascular endothelial cells, HPMEC • immunoglobulin, Ig • low-density lipoprotein, LDL • LDL receptor, LDLR • lactoferrin, LTF • native LDL, nLDL • monoclonal antibody, mAb • mean fluorescence units, MFU • oxidized LDL, oxLDL • platelet activating factor, PAF • percent positively labeled cells, %POS • red blood cells, RBC This article has been cited by other articles:
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