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Am J Physiol Cell Physiol (October 16, 2002). doi:10.1152/ajpcell.00177.2002
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Articles in PresS, published online ahead of print October 16, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00177.2002
Submitted on April 17, 2002
Accepted on October 14, 2002

Uptake of modified low-density lipoproteins alters actin distribution and locomotor forces in macrophages

Celina V Zerbinatti1* and Robert W Gore2

1 Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, USA
2 Department of Physiology, University of Arizona, Tucson, AZ, USA

* To whom correspondence should be addressed. E-mail: zerbinatti_c{at}kids.wustl.edu.

It is postulated that macrophage-derived foam cells accumulate in the arterial wall because they lose the ability to migrate after excessive ingestion of modified forms of low-density lipoproteins (LDL). To access changes in locomotor force generating capacity of foam cells, we measured isometric forces in J774A.1 macrophages after cholesterol loading with oxidized (Ox-LDL) or aggregated (Agg-LDL) LDL using a novel magnetic force transducer. Ox-LDL loading reduced the ability of J774A.1 macrophages to generate isometric forces by 50% relative to control cells; changes in force frequency consistent with reduced motility were detected as well. Agg-LDL loading was also detrimental to J774A.1 motility, but to a lesser extent than Ox-LDL. Ox-LDL loading significantly reduced total actin levels and induced changes in the F-actin to G-actin distribution, while Agg-LDL loaded cells had significantly increased levels of total actin. These data provide evidence that cholesterol loading and subsequent accumulation decreases macrophage motility by reducing the cells' force generating capacity, and that Ox-LDL appears to be more effective than Agg-LDL in disrupting the locomotor machinery.




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