Lipoprotein lipase deficiency in mice resulted in an approximately 40% reduction in blood white blood cells, neutrophils, and inflammatory monocytes, impairing bone marrow myelopoiesis.
Does Lipoprotein lipase deficiency impair bone marrow myelopoiesis and reduce circulating monocyte levels in mice?
Lipoprotein lipase regulates peripheral leukocyte levels and affects bone marrow monocyte progenitor differentiation and aortic macrophage accumulation, highlighting its role in inflammatory responses related to cardiovascular disease.
Effect estimate: ≈40% reduction
Objective— Tissue macrophages induce and perpetuate proinflammatory responses, thereby promoting metabolic and cardiovascular disease. Lipoprotein lipase (LpL), the rate-limiting enzyme in blood triglyceride catabolism, is expressed by macrophages in atherosclerotic plaques. We questioned whether LpL, which is also expressed in the bone marrow (BM), affects circulating white blood cells and BM proliferation and modulates macrophage retention within the artery. Approach and Results— We characterized blood and tissue leukocytes and inflammatory molecules in transgenic LpL knockout mice rescued from lethal hypertriglyceridemia within 18 hours of life by muscle-specific LpL expression (MCKL0 mice). LpL-deficient mice had ≈40% reduction in blood white blood cell, neutrophils, and total and inflammatory monocytes (Ly6C/G hi ). LpL deficiency also significantly decreased expression of BM macrophage-associated markers (F4/80 and TNF-α tumor necrosis factor α), master transcription factors (PU.1 and C/EBPα), and colony-stimulating factors (CSFs) and their receptors, which are required for monocyte and monocyte precursor proliferation and differentiation. As a result, differentiation of macrophages from BM-derived monocyte progenitors and monocytes was decreased in MCKL0 mice. Furthermore, although LpL deficiency was associated with reduced BM uptake and accumulation of triglyceride-rich particles and macrophage CSF–macrophage CSF receptor binding, triglyceride lipolysis products (eg, linoleic acid) stimulated expression of macrophage CSF and macrophage CSF receptor in BM-derived macrophage precursor cells. Arterial macrophage numbers decreased after heparin-mediated LpL cell dissociation and by genetic knockout of arterial LpL. Reconstitution of LpL-expressing BM replenished aortic macrophage density. Conclusions— LpL regulates peripheral leukocyte levels and affects BM monocyte progenitor differentiation and aortic macrophage accumulation.
Chang et al. (Thu,) conducted a other in Lipoprotein lipase deficiency. Lipoprotein lipase deficiency (genetic knockout) was evaluated on Blood white blood cell, neutrophils, and total and inflammatory monocytes (≈40% reduction). Lipoprotein lipase deficiency in mice resulted in an approximately 40% reduction in blood white blood cells, neutrophils, and inflammatory monocytes, impairing bone marrow myelopoiesis.