Degranulation of cutaneous mast cells induces transendothelial transport and local accumulation of plasma LDL in rat skin in vivo.
In severe hypercholesterolemia and sometimes even in normolipemia, lipoprotein-derived cholesterol accumulates in the skin, forming xanthomas, but the local factors triggering this accumulation are not known. We therefore studied the effect of immunoglobulin E (IgE)-mediated stimulation of cutaneous mast cells on the transport of low density lipoprotein (LDL) from plasma to skin during the passive cutaneous anaphylaxis (PCA) reaction in rats. PCA sites were produced in rats by giving intracutaneous injections of rat serum containing high levels of IgE antibodies against ovalbumin. When ovalbumin was then injected intravenously into the rats, the skin histamine content at the sensitized skin sites decreased, reflecting degranulation of the passively sensitized (IgE-containing) mast cells at these sites, with ensuing release of histamine from the mast cells. Concomitant intravenous injection of increasing amounts of human [14C]sucrose-LDL led to rapid and dose-dependent increases in the skin [14C]sucrose-LDL content. These (maximally about 40-fold) increases were strictly localized to the PCA reaction sites: no such increase in [14C]sucrose-LDL content was observed in nonsensitized skin areas or in any other tissue of the rats. The increase in skin [14C]sucrose-LDL content could be blocked (by about 80%) with a combination of H1 and H2 receptor antagonists, and could be mimicked by intradermal injection of histamine. This study demonstrates an increase in plasma LDL influx into the skin at sites where mast cells are stimulated, and so suggests that mast cells play a role in the accumulation of LDL cholesterol that occurs in the skin when xanthomas form.
Ma
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Wihuri Research Institute, Helsinki, Finland.
Kovanen
P T
PT
D000818:Animals; D001693:Biological Transport, Active; D015550:Cell Degranulation; D004730:Endothelium, Vascular / Q000378:metabolism; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000502:physiology*; D010323:Passive Cutaneous Anaphylaxis; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013395:Sucrose / Q000097:blood / Q000378:metabolism; D014973:Xanthomatosis / Q000209:etiology / Q000378:metabolism
C035247:LDL-sucrose; D008077:Lipoproteins, LDL; D007073:Immunoglobulin E; D013395:Sucrose