Effects of calcium on the migration and recruitment of macrophages and macrophage-derived foam cells.
Calcium is thought to play an important role in the genesis of atherosclerotic lesions, but the precise mechanisms involved are unclear. In the present investigation, we have used in vitro systems to investigate the effects of calcium on one key aspect of lesion development: the migration of macrophages and macrophage/foam cells. Using agarose plate migration assays, the migratory characteristics of macrophages exposed to 1) no lipoprotein, 2) low density lipoprotein (LDL), 3) acetylated low density lipoprotein (acLDL), and ) oxidized low density lipoprotein were examined. The most marked stimulatory effect on macrophage mobility was observed when freshly isolated cells were exposed to acLDL during the migration assay. High levels of exogenous calcium were found to suppress the stimulatory effect of acLDL on migration. As the responses of macrophages exposed to a uniform concentration of agents in the surrounding medium may differ from chemotactic responses to a concentration gradient, the migration of macrophages, with and without preexposure to acLDL or LDL, was studied using microchemotaxis Boyden chambers. Under these conditions, calcium acted as a highly potent chemoattractant, especially to cells that had been preincubated with acLDL. These results suggest how elevated external calcium concentration leads initially to macrophage recruitment, and subsequently to foam cell aggregation and lipid core formation, in association with calcification, in the developing atherosclerotic plaque.
Shi
H
H
Institute for Arteriosclerosis Research, University of Münster, Germany.
Severs
N J
NJ
Robenek
H
H
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002114:Calcinosis / Q000209:etiology; D002118:Calcium / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis; D005487:Foam Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017275:Isradipine / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice
D008074:Lipoproteins; D002118:Calcium; D017275:Isradipine