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Control of lipoprotein lipase secretion by macrophages: effect of macrophage differentiation agents
1Department of Membrane Research, Weizmann Institute of Science, Rehovot, Israel.
Abstract:
The effect of macrophage differentiation agents on lipoprotein lipase (LPL) secretion by macrophages at different stages of differentiation/maturation was investigated. Phorbol myristate acetate (TPA) had an augmenting effect on LPL secretion by in vitro-derived bone marrow macrophages (BMMs), thioglycollate-elicited peritoneal macrophages (TgM phi), and resistant macrophages. Augmentation was time dependent and reached approximately two-fold and approximately threefold increase over control cells within 16 and 96 hr, respectively. TPA did not affect LPL secretion from J774.1 cells treated with the agent for 16-72 hr. L-cell conditioned medium (L-CM), a source of macrophage colony-stimulating activity, augmented LPL secretion by BMMs and Tg-M phi, and when added together with TPA had an additive augmenting effect on LPL secretion in these cells. Retinoic acid (RA) exerted a time-dependent suppressive effect on LPL secretion by BMMs (46% within 16 hr and 83% within 6 d), had a relatively small effect on secretion from J774.1 cells (approximately 20% in 72 hr) and had no effect on LPL secretion by Tg-M phi. Dexamethasone suppressed LPL secretion by BMMs, Tg-M phi, and J774.1 cells. Optimal suppression of LPL secretion by BMMs required more than 24 hr. Thus, TPA and L-CM, agents that exert a mitogenic effect on BMMs and Tg-M phi, augmented the secretion of LPL in these cell types, and RA and dexamethasone, agents which induce differentiation patterns in myeloid cells, suppressed LPL secretion.
Insights
Macrophage differentiation agents differentially affect lipoprotein lipase (LPL) secretion. Mitogenic agents like TPA and L-CM augmented LPL secretion, while differentiation agents like retinoic acid and dexamethasone suppressed it.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Lipoprotein lipase (LPL) plays a crucial role in lipid metabolism.
- Macrophages are key immune cells involved in various physiological and pathological processes.
- Understanding how macrophage differentiation affects LPL secretion is important for metabolic and inflammatory research.
Purpose of the Study:
- To investigate the impact of various macrophage differentiation agents on lipoprotein lipase (LPL) secretion.
- To determine the differential effects of mitogenic and differentiation-inducing agents on LPL secretion at different macrophage maturation stages.
Main Methods:
- Primary macrophages (bone marrow-derived macrophages and thioglycollate-elicited peritoneal macrophages) and a macrophage cell line (J774.1) were used.
- Cells were treated with phorbol myristate acetate (TPA), L-cell conditioned medium (L-CM), retinoic acid (RA), and dexamethasone.
- Lipoprotein lipase (LPL) secretion levels were measured over time.
Main Results:
- TPA and L-CM augmented LPL secretion in a time-dependent manner in primary macrophages.
- Retinoic acid (RA) and dexamethasone suppressed LPL secretion in a time-dependent manner in primary macrophages and J774.1 cells.
- TPA did not affect LPL secretion in J774.1 cells, while RA and dexamethasone showed varying degrees of suppression across cell types.
Conclusions:
- Mitogenic agents (TPA, L-CM) promote LPL secretion in macrophages.
- Differentiation agents (RA, dexamethasone) suppress LPL secretion, indicating a complex regulatory relationship.
- Macrophage differentiation status significantly influences the response to external stimuli regarding LPL secretion.