Bactericidal permeability-increasing protein precursor (BPI) (CAP 57)
развернуть
High TARC plasma levels confer protection to long living individuals by inducing M2 profile.
A way to delay aging and the related low-grade chronic inflammatory state is to study the model of positive physiology such as the Long-Living Individuals (LLIs). Our recent studies have shown higher levels of the host defense BPI Fold-Containing Family B Member 4 (BPIFB4) protein in the LLIs' blood. Notably, BPIFB4 has been shown to influence monocytes typesetting and M2 anti-inflammatory phenotype (CD206 CD163 ) macrophages skewing. According to the role of a complex cytokine milieu in guiding the macrophage polarization, here we found that circulating concentrations of thymus and activation regulated chemokine (TARC)/CCL17 and small-inducible cytokine B10 (IP-10)/CXCL10) cytokines, were additionally associated with the LLIs' state. In a differentiation process in vitro, the addition of LLIs' plasma to the cell culture medium, enhanced the ability of monocytes, either from LLIs or controls, to acquire a M2 phenotype. Interestingly, a neutralizing antibody against TARC blunted the M2 skewing effect of the LLIs' plasma. Collectively, these data indicate that exceptional longevity may associate with a peculiar anti-inflammatory myeloid profile responsible for improved reparative processes and reduced inflammatory status mediated in part by TARC and M2 generation.
Keywords
- FACS
- Longevity
- M2 macrophages
- Plasma profile
- TARC
развернуть
Circulating
BPIFB4 Levels Associate With and Influence the Abundance of Reparative Monocytes and Macrophages in Long Living Individuals.
Long-Living Individuals (LLIs) delay aging and are less prone to chronic inflammatory reactions. Whether a distinct monocytes and macrophages repertoire is involved in such a characteristic remains unknown. Previous studies from our group have shown high levels of the host defense BPI Fold Containing Family B Member 4 (BPIFB4) protein in the peripheral blood of LLIs. Moreover, a polymorphic variant of the [i]BPIFB4[/i] gene associated with exceptional longevity ([i]LAV-BPIFB4[/i]) confers protection from cardiovascular diseases underpinned by low-grade chronic inflammation, such as atherosclerosis. We hypothesize that BPIFB4 may influence monocytes pool and macrophages skewing, shifting the balance toward an anti-inflammatory phenotype. We profiled circulating monocytes in 52 LLIs (median-age 97) and 52 healthy volunteers (median-age 55) using flow cytometry. If the frequency of total monocyte did not change, the intermediate CD14 CD16 monocytes counts were lower in LLIs compared to control adults. Conversely, non-classical CD14 CD16 monocyte counts, which are M2 macrophage precursors with an immunomodulatory function, were found significantly associated with the LLIs' state. In a differentiation assay, supplementation of the LLIs' plasma enhanced the capacity of monocytes, either from LLIs or controls, to acquire a paracrine M2 phenotype. A neutralizing antibody against the phosphorylation site (ser 75) of BPIFB4 blunted the M2 skewing effect of the LLIs' plasma. These data indicate that LLIs carry a peculiar anti-inflammatory myeloid profile, which is associated with and possibly sustained by high circulating levels of BPIFB4. Supplementation of recombinant BPIFB4 may represent a novel means to attenuate inflammation-related conditions typical of unhealthy aging.
Keywords
- FACS
- M2 macrophages
- immunity
- longevity
- patrolling-monocytes
- plasma
{{medline-entry
|title=The effect of postural deformities on back function and pain in patients with Parkinson's disease.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31177242
|abstract=Postural deformities, such as Pisa syndrome (PS), and camptocormia and antecollis (C