The mast cell as a pluripotent HDL-modifying effector in atherogenesis: from in vitro to in vivo significance.
OBJECTIVE
The purpose of this review is to summarize evidence about the effects that mast cell mediators can exert on the cholesterol efflux-inducing function of high density lipoproteins (HDL).


RESULTS
Subendothelially located activated mast cells are present in inflamed tissue sites, in which macrophage foam cells are also present. Upon activation, mast cells degranulate and expel 2 major neutral proteases, chymase and tryptase, and the vasoactive compound histamine, all of which are bound to the heparin-proteoglycan matrix of the granules. In the extracellular fluid, the proteases remain heparin-bound and retain their activities, whereas histamine dissociates and diffuses away to reach the endothelium. The heparin-bound mast cell proteases avidly degrade lipid-poor HDL particles so preventing their ability to induce cholesterol efflux from macrophage foam cells. In contrast, histamine enhances the passage of circulating HDL through the vascular endothelium into interstitial fluids, so favoring HDL interaction with peripheral macrophage foam cells and accelerating initiation of macrophage-specific reverse cholesterol transport.


CONCLUSIONS
Mast cells exert various modulatory effects on HDL function. In this novel tissue cholesterol-regulating function, the functional balance of histamine and proteases, and the relative quantities of HDL particles in the affected microenvironment ultimately dictate the outcome of the multiple mast cell effects on tissue cholesterol content.
Wihuri Research Institute, Helsinki, Finland.
Miriam
M
Lee-Rueckert
Petri T
PT
Kovanen
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D002199:Capillary Permeability; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008407:Mast Cells / Q000502:physiology*; D059748:Proteolysis
D008075:Lipoproteins, HDL; D002784:Cholesterol