CD11b/CD18 mediates production of reactive oxygen species by mouse and human macrophages adherent to matrixes containing oxidized LDL.
Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages adherent to matrix proteins that contain or have been modified by oxidized LDL (oxLDL) may play an important role in atherogenesis. In vitro, human macrophages adhere to matrixes containing oxLDL via scavenger receptors and are signaled to produce ROS partly by interactions of the class B scavenger receptor (SR-B) CD36 with ligands on the matrix. In this report, we show that macrophages from mice genetically deficient in SR-A or CD36 adhered equally as well and produced equal amounts of ROS on interaction with matrix-associated oxLDL. In contrast, macrophages from mice genetically deficient in the CD18 chain of beta(2)-integrins produced insignificant amounts of ROS on interaction with oxLDL-containing matrixes, even though they adhered to these matrixes as efficiently as did macrophages from wild-type mice. Antibodies against CD18, CD11b, or EDTA, the last of which chelates divalent cations required for integrin function, had no effect on adhesion of normal mouse or human macrophages to matrixes containing oxLDL but almost completely inhibited ROS production by macrophages adherent to this matrix. Thus, CD11b/CD18 plays an important role in regulating production of ROS by mouse and human macrophages adherent to matrixes containing oxLDL. It may play a hitherto-unsuspected role in regulating macrophage signaling pathways involved in inflammation and atherogenesis.
Husemann
J
J
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. jh577@columbia.edu
Obstfeld
A
A
Febbraio
M
M
Kodama
T
T
Silverstein
S C
SC
D000818:Animals; D001161:Arteriosclerosis; D018845:CD11 Antigens / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D018845:CD11 Antigens; D018821:CD18 Antigens; D016326:Extracellular Matrix Proteins; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein