Number Of Apoptotic Macrophages Research Articles

Human Perifollicular Macrophages Undergo Apoptosis, Express Wnt Ligands, and Switch their Polarization during Catagen

Human Perifollicular Macrophages Undergo Apoptosis, Express Wnt Ligands, and Switch their Polarization during Catagen

Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3

In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr−/−) mice with macrophage-specific loss of Trpc3 (MacTrpc3−/−/Ldlr−/− → Ldlr−/−). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3−/−/Ldlr−/− → Ldlr−/− mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis.

Inflammatory and immuno-reactivity in mice induced by intramuscular implants of HSNGLPL peptide grafted-polyurethane.

Synthetic peptide-based polyurethanes (PUs), introduced as bioactive agents and possessing impressive properties, have emerged as attractive functional biomaterials for tissue regeneration. In this study, we developed a PU with a pendent HSNGLPL group through click reaction, which has strong affinity to TGF-β1. The peptide grafted-PUs, or PUs with BDO as the chain extender (control), were implanted into the gastrocnemius muscle (GN) of C57BL/6 mice, for evaluating their inflammatory and immuno-reactivity in vivo. We show herein that, after muscle implantation, BDO-PU induced a conspicuous monocyte/macrophage infiltration and myofiber degeneration. The inflammatory invasion and myofiber necrosis were mainly detected in the site around, but not far from, the implants, suggesting that the degraded PU matrix only triggers a local and limited inflammation in vivo. In contrast, peptide grafted-PU induced intramuscular inflammation was more complex and was sustained for more than 2 months. Apart from nonspecific monocyte/macrophage infiltration as in the case of BDO-PU, CD4+ T cells and dendritic cells (DCs), the members of the adaptive immune system, can be detected within the inflammatory site around peptide grafted-PU implants. The number of apoptotic macrophages in muscle containing peptide-PU was significantly lower compared to that in muscle containing BDO-PU. Thus, our present results suggest that, the PU matrix degradation-produced local environment is toxic to muscle cells and induces muscle degeneration. Moreover, highly aggregated peptide on PU might act as an immunogen to trigger intramuscular inflammation and lead to the delayed inflammatory response.

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3(-/-);Ldlr(-/-) mice were no different from RIP3(+/+);Ldlr(-/-) mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe(-/-) background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3(-/-);Ldlr(-/-) and RIP3(+/+);Ldlr(-/-) mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3(-/-) mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL)-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.