Researchers have found evidence for a role of insulin-like growth factor derived from immune cells called macrophages in increasing the uptake of microvesicles by non-professional phagocytes, such as fibroblasts and airway epithelial cells, thereby decreasing tissue inflammation.


Our bodies clear billions of cells that die by apoptosis on a daily basis through the actions of both neighboring tissue cells (‘non-professional phagocytes’) such as fibroblasts or epithelial cells, and tissue-resident and recruited ‘professional phagocytes’ such as macrophages and dendritic cells. Even though non-professional and professional macrophages exist in close proximity in most tissues, it is not well understood whether they communicate with each other during the clearance of dying cells, and how this may influence tissue inflammation.

In a new study published in the journal Nature, researchers found that macrophages (professional phagocytes) change the kind of particles taken up by non-professional phagocytes (i.e. epithelial cells) and affect their inflammatory response, through the release of a soluble growth factor and microvesicles. They showed that macrophages secreted insulin-like growth factor 1 (IGF-1) during phagocytosis of apoptotic cells or in response to inflammation-related cytokines. Moreover, the binding of IGF-1 on non-professional phagocytes to its receptor altered their phagocytosis, in such a way that there was reduced uptake of larger apoptotic cells while enhanced engulfment of microvesicles. IGF-1 did not change engulfment by macrophages. Macrophages also secreted microvesicles, whose uptake by epithelial cells was increased by IGF-1 and resulted in reduced inflammatory responses by epithelial cells. Consistent with these results, the researchers discovered that deletion of IGF-1 receptor in airway epithelial cells resulted in worsened lung inflammation after exposure to allergens.

In summary, the findings show that IGF-1- and microvesicle- dependent communication between epithelial cells and macrophages can significantly affect the extent of tissue inflammation in vivo. The evidence pinpoints a two-part regulation by macrophages of epithelial cells that influences airway inflammation, specifically, the release of soluble IGF-1 from macrophages redirects particle uptake, and the release of microvesicles decreases inflammatory cytokine production by epithelial cells.



Written by: Nigar Celep, BASc

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