Published ahead of print on May 30, 2003, doi:10.1165/rcmb.2002-0257OC Am. J. Respir. Cell Mol. Biol., Volume 29, Number 6, December 2003, 702-709 A more recent version of this article appeared on December 1, 2003
Submitted on November 19, 2002 Oxidized low density lipoprotein activates migration and degranulation of human granulocytesJulie B Sedgwick1*,1 Allergy and Immunology, Department of Medicine, University of Wisconsin, Madison, WI, USA, 2 College of Medicine, Gyeongsang National University, Chinju, Korea, Republic of, 3 Allergic Disease Research, Mayo Clinic, Rochester, MN, USA * To whom correspondence should be addressed. 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 oxidized (ox)LDL 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 100µg/ml oxLDL vs 2.9±1.1% for buffer, p<0.05) and eosinophil (19.3±3.5% vs 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-1
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activated human pulmonary microvascular endothelial cell monolayers was similarly stimulated by xLDL. OxLDL activated significant degranulation of both neutrophils (100.9±9.8 vs 49.6±8.4 ng lactoferrin released/5x105 neutrophils for buffer, p<0.05) and eosinophils (342±115.4 vs 85.8±30.4 ng eosinophil derived neurotoxin/1x106 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 granulocyte are recruited to the lung.
