Intracellular distribution of ibuprofen within monocytes.
The interaction of ibuprofen (CAS 15687-27-1) with muscle proteins was investigated in vitro and binding to actin was found to be more marked than to other muscle proteins. Actin polymerization, however, was not influenced by this interaction. The kinetics of ibuprofen internalization by human monocytes/macrophages from peripheral blood at 37 degrees C and its partitioning to different cellular compartments was studied and compared to the actin content of these subcellular fractions. The bulk of cell-bound ibuprofen (89.7%) was found in the cell debris fraction (1,000 g sediment), 7.3% were recovered in the 10,000 g sediment, only 0.5% in the 100,000 g sediment and 2.5% in the cytosolic fraction. The distribution of F-actin to the different subcellular fractions was verified by fluorescence analysis using NBD-phallacidin. Four times more F-actin was found in the 1,000 g sediment than in the 10,000 g fraction, while the microsomal fraction contained only 8% of total F-actin. In the cytosol, significant amounts of soluble actin were detected. These data indicate that ibuprofen could theoretically interact with actin in all the cellular subfractions to which it is distributed after internalization.
Menzel
E J
EJ
Institute of Immunology, University of Vienna, Austria.
Binder
M
M
Kolarz
G
G
D000199:Actins / Q000096:biosynthesis / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003956:Dialysis; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000378:metabolism; D015388:Organelles / Q000378:metabolism; D011485:Protein Binding
D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009124:Muscle Proteins; D007052:Ibuprofen