Premium
Distinct Roles of Apolipoprotein A1 and Lecithin‐Cholesterol Acyltransferase in Lipopolysaccharide‐Induced Inflammation
Author(s) -
Petropoulou P.I.,
Berbée J.,
Hatziri A,
Karagiannides I.,
Kypreos K.
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.715.16
Subject(s) - lipopolysaccharide , inflammation , endocrinology , medicine , monocyte , acyltransferase , lymphocyte , chemistry , biochemistry , enzyme
Aim We studied lipopolysaccharide (LPS)‐induced inflammation under conditions of Apoa1‐ or Lcat‐ deficiency. Methods RAW 264.7 macrophages, whole blood and peritoneal macrophages from C57BL/6 (WT), Lcat‐deficient ( Lcat ‐/‐ ) and Apoa1‐deficient ( Apoa1 ‐/‐ ) mice were challenged with LPS and plasma TNFα was measured. WT, Lcat ‐/‐ and Apoa1 ‐/‐ mice were challenged intravenously with LPS and plasma cytokines were monitored. WT, Lcat ‐/‐ and Apoa1 ‐/‐ leukocytes were phenotyped using FACS. Results Serum and HDL from Lcat ‐/‐ and Apoa1 ‐/‐ mice display reduced capacity to attenuate the LPS‐induced TNFα response, in vitro . Blood from Lcat ‐/‐ and Apoa1 ‐/‐ mice show an increased TNFα response when stimulated with LPS ex vivo, with more pronounced effect for Lcat ‐/‐ blood. Lcat ‐/‐ and Apoa1 ‐/‐ mice show a markedly enhanced and prolonged LPS‐induced inflammatory response in vivo . LCAT‐deficiency is associated with leukocytosis, increased CD11b + /Ly‐6C med monocyte and CD4 + lymphocyte levels, but low CD11b + /Ly‐6C hi monocyte levels and CD11b expression. Similarly, peritoneal macrophages from Lcat ‐/‐ mice show reduced LPS‐induced TΝFα response. In contrast, APOA1 deficiency is associated with decreased leukocyte, CD11b + /Ly‐6C lo/med/hi monocyte and CD4 + , CD8 + lymphocyte levels. Conclusions LCAT deficiency renders leukocytes less responsive to LPS, but increases their number in circulation, while APOA1 deficiency results in fewer but more responsive leukocytes.