Low density lipoprotein oxidized in xanthoma tissue induces the formation and infiltration of foam cells.
Human low density lipoprotein (LDL) was incubated with rabbit xanthoma tissue or non-lesional dermis. The xanthoma tissue-modified LDL (x-LDL) was oxidized showing a 12-fold higher level of thiobarbituric acid-reactive substances (TBARSs) and a faster anodic electrophoretic mobility than native LDL (n-LDL). The LDL treated with non-lesional dermis (d-LDL) had a twofold higher TBARS level compared with n-LDL, but the electrophoretic mobility of d-LDL and n-LDL was similar. Cholesterol esterifying activity in mouse peritoneal macrophages, an indicator of LDL uptake, was up-regulated 5-fold and 1.8-fold by incubation with x-LDL and d-LDL, respectively, compared with n-LDL. Macrophages transformed into foam cells in incubation with x-LDL, and intradermal injections of x-LDL induced infiltration of great many foam cells in the normolipemic rabbit dermis. d-LDL had much less effects on the foam cell formation and foam cell infiltration than x-LDL. Cholesterol:protein ratio was higher in x-LDL than in n-LDL and d-LDL, suggesting that x-LDL-induced foam cells accumulated the lipids by incorporating the cholesterol-rich x-LDL. In conclusion, extravasated LDL receives oxidation and contributes to foam cell recruitment in xanthoma lesions. On the other hand, extravasated LDL in non-lesional dermis receives limited oxidation and additional promoting factors are necessary for initiation of xanthoma development.
Hirata
Yasuhiko
Y
Department of Dermatology, Kochi Medical School, Okohcho, Nankoku, Kochi 783-8505, Japan. ikedamit@kochi-ms.ac.jp
Okawa
Kozo
K
Ikeda
Mitsunori
M
Seike
Masahiro
M
Matsumoto
Masaaki
M
Kodama
Hajime
H
D000818:Animals; D005260:Female; D005487:Foam Cells / Q000473:pathology*; D006801:Humans; D007271:Injections, Intradermal; D008077:Lipoproteins, LDL / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D012867:Skin / Q000473:pathology; D014973:Xanthomatosis / Q000378:metabolism* / Q000473:pathology*
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein