Related Experiment Videos
Angiogenic macrophages produce the angiogenic inhibitor thrombospondin 1
1Department of Pathology, Northwestern University, Chicago, Illinois.
Abstract:
Previous investigations have shown that macrophages play a pivotal role in the induction of angiogenesis in both physiological and pathological settings. This investigation examines the relative production of the angiogenic modulator thrombospondin-1 (TSP1) by activated and nonactivated monocytes and macrophages. TSP1, a multifunctional extracellular matrix molecule, has been reported recently to inhibit angiogenesis both in vitro and in vivo. To examine the relationship between the level of TSP1 production by macrophages and expression of the angiogenic phenotype, murine monocytelike cells (WEHI-3) and human peripheral blood monocytes were each activated in vitro and examined for TSP1 production and angiogenic activity in rat corneal bioassay. Nonangiogenic monocytes produced low levels of TSP1 messenger RNA. Surprisingly, activated, potently angiogenic monocytes and macrophages exhibited as much as a sixfold increase in steady state TSP1 messenger RNA over unstimulated levels. Biosynthetic labeling studies demonstrated that TSP1 protein secretion increased in conjunction with increased TSP1 messenger RNA levels in angiogenic macrophages. The results demonstrate that activated monocytes and macrophages actively produce the angiogenic modulator TSP1 and suggest that TSP1 production may be a component of the angiogenic phenotype. In addition, the data suggest that the ability of macrophages to mediate angiogenesis results from a complex interplay of positive and negative regulators.
Insights
Activated macrophages surprisingly increase production of thrombospondin-1 (TSP1), an angiogenesis inhibitor. This suggests TSP1 is part of the angiogenic phenotype, highlighting a complex interplay of regulators in macrophage-mediated angiogenesis.
Area of Science:
- Cell Biology
- Immunology
- Angiogenesis Research
Background:
- Macrophages are crucial for angiogenesis in various conditions.
- Thrombospondin-1 (TSP1) is an extracellular matrix molecule known to inhibit angiogenesis.
- The role of TSP1 production by macrophages in angiogenesis is not fully understood.
Purpose of the Study:
- To investigate the production of thrombospondin-1 (TSP1) by activated and nonactivated monocytes and macrophages.
- To determine the relationship between TSP1 production levels and the angiogenic phenotype of macrophages.
Main Methods:
- Murine monocyte-like cells (WEHI-3) and human peripheral blood monocytes were activated in vitro.
- TSP1 messenger RNA (mRNA) levels were quantified using quantitative PCR.
- TSP1 protein secretion was assessed via biosynthetic labeling.
- Angiogenic activity was evaluated using a rat corneal bioassay.
Main Results:
- Nonangiogenic monocytes produced low levels of TSP1 mRNA.
- Activated, angiogenic monocytes and macrophages showed a significant increase (up to sixfold) in steady-state TSP1 mRNA levels.
- Increased TSP1 mRNA levels correlated with enhanced TSP1 protein secretion in angiogenic macrophages.
Conclusions:
- Activated monocytes and macrophages actively produce the angiogenesis modulator TSP1.
- TSP1 production appears to be a component of the angiogenic phenotype in these cells.
- Macrophage-mediated angiogenesis likely results from a complex balance of positive and negative regulatory factors.