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Conformational changes in oxidized LDL recognized by mouse peritoneal macrophages
1Department of Biochemistry, Teikyo University School of Medicine, Tokyo, Japan.
Biochimica Et Biophysica Acta
|November 17, 1994
Summary
Mouse macrophages engulf aggregated oxidized LDL, not native LDL. This uptake is linked to Schiff base formation and autofluorescence, suggesting a specific recognition mechanism for oxidized LDL conformational changes.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Macrophages recognize oxidized LDL via scavenger receptors.
- Conformational changes in oxidized LDL driving this recognition remain unclear.
Purpose of the Study:
- To investigate the conformational changes in oxidized LDL that influence macrophage uptake.
- To identify the specific forms of oxidized LDL preferentially ingested by macrophages.
Main Methods:
- Oxidized LDL (oxLDL) autofluorescence analysis (Ex:365 nm Em:430 nm) at varying pH.
- HPLC fractionation of oxLDL into native and aggregated particles.
- Macrophage uptake assays with native and aggregated oxLDL, assessing inhibition by heparin and cytochalasin B.
Main Results:
- Macrophage uptake of oxLDL correlated with its autofluorescence intensity.
- Fluorescent products in oxLDL exhibited Schiff base characteristics, pH-dependent.
- Macrophages selectively ingested aggregated oxLDL, not native-sized oxLDL.
- Heparin and cytochalasin B significantly suppressed aggregated oxLDL uptake.
Conclusions:
- Mouse peritoneal macrophages recognize oxLDL conformational changes associated with Schiff base formation and increased autofluorescence.
- Macrophages preferentially phagocytose aggregated oxLDL particles.
- The uptake mechanism involves scavenger receptors and phagocytosis, modulated by heparin-sensitive pathways.