Signalling shutdown strategies in aging immune cells

Abstract

SummaryIt is important for the resolution of inflammation that the number and activity of immune cells are reduced. Clearance of immune cells may be achieved by apoptosis and phagocytosis of cell fragments by macrophages. However, signalling shutdown by immune cells committed to apoptosis occurs early in the progression of these cells towards fragmentation and, it could be argued, is a key feature of apoptosis. There is surprisingly little known about the mechanisms that underlie this signalling shutdown, in particular the shutdown of Ca 2+ influx. The consequences and the potential mechanisms by which Ca 2+ influx shutdown is achieved are discussed. In addition, the potential consequences for cell signalling of cytochrome c release from mitochondria and of phosphatidylserine externalization are discussed. The aim of the review is therefore to highlight the evidence for various signalling shutdown strategies in immune cells that may limit their activity during progression towards apoptosis.

Human microparticles generated during sepsis in patients with critical illness are neutrophil-derived and modulate the immune response

“…Previous studies have shown that MPs contain PS on their cell surface, a signal for phagocytosis. 16–18 Our data demonstrate that NDMPs are indeed phagocytosed by THP-1 cells and that this phagocytosis has a divergent, and potentially important, effect on the immune system. Cells that had ingested NDMPs had increased activation and phagocytic ability as compared with both cells not exposed to NDMPs and bystander cells.…”

“…16,17 PS is also a signal for phagocytosis (as reviewed by Ayub and Hallett 18 ) . This led us to examine whether NDMPs are actively phagocytosed.…”

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

“…Calcium binding is important for a variety of eukaryotic calcium signalling systems of macrophages involved in the phagocytosis of bacteria [37][38][39][40]. Consequently, inhibition of calcium binding by a phenothiazine inhibits calcium signalling processes and therefore the processes of post-phagocytosis should be affected.…”

Linking the FMR1 alleles with small CGG expansions with neurodevelopmental disorders: Preliminary data suggest an involvement of epigenetic mechanisms

“…Further, we found that the over-expression of FMR1 was significantly correlated with the expression of DNMT1, and there was a marginally significant relationship between the expression levels of DNMT1 and CYC1, the latter being a marker of mitochondrial dysfunction [Li et al,1996; Ayub & Hallett, 2004]. These findings are suggestive of epigenetic involvement in GZ alleles, and are supportive of the results obtained for PM alleles from a human kidney fibroblast cell line (HEK293), where insertion of 176 CGG repeats 3’ of the FMR1 promoter induced over-expression of FMR1 mRNA, and altered expression of major epigenetic factors, which was associated with increased apoptosis [Handa et al, 2005].…”