@alex3619 I too haven't thought about that and like you find it very interesting!
I listened to Prof. Pete Smith make his comment [about 36.28 on the video] and checked PubMed for two mast cell papers he might have been referring to, but that wasn't too clear on the video:
https://www.ncbi.nlm.nih.gov/pubmed/27362406
https://www.ncbi.nlm.nih.gov/pubmed/29223146
Papers seem to say mast cells circulate in immature form in the circulation and ordinarily not in mature form. Their researchers found activated mast cells in patients and more mast cell progenitor cells circulating in the blood than in controls.
Interestingly, doing a quick internet search I see that large-scale mast cell degranulation-- cells burst and spill their contents-- can cause
"hypovolemia" (low blood volume), hypotension, vascular permeability, and other symptoms. Also
"exercise" can trigger mast cell activation. Astronauts get hypovolemia in space which resolves when they return to the gravity on earth; perhaps this is how it occurs in those of us earth-bound!
So now I'm wondering (1) as you point out Alex whether any mast cell contents might be in the plasma getting through the filter
@ljimbo423 indicates Ron Davis used; and (2) whether cytokines Dr. Montoya measured after exercise might have come from mast cell activation due to the exercise.
Also be nice to know if Maureen Hanson's planned exercise research will include mast cells (she said at the London Conference she'd be looking at immune cells
by type) and that Dr. Chia would be collaborating. Could that be to examine the tissue microenvironment where one might find viruses and mature mast cells?
So many questions and excellent research going on!
I asked Smith about the Mast cell research and he says it is from these two papers:
Asian Pac J Allergy Immunol.2017 Dec 10. doi: 10.12932/AP-200517-0086. [Epub ahead of print]
Investigation of mast cell toll-like receptor 3 in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Systemic Mastocytosis participants using the novel application of autoMACS magnetic separation and flow cytometry.
Balinas C1,2,
Nguyen T1,2,
Johnston S1,2,
Smith P2,
Staines D1,2,
Marshall-Gradisnik S1,2.
Author information
Abstract
BACKGROUND:
Viral infections and hypersensitivities are commonly reported by Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. Mast Cells (MC) uniquely mediate type 1 hypersensitivities and resolve viral infections via toll-like receptor 3 (TLR3).
OBJECTIVE:
To characterise and compare mast cell progenitors (MCPs) in CFS/ME participants with a known MC disorder, Systemic mastocytosis (SM), and secondly, to investigate the role of MC TLR3 in CFS/ME participants following Polyinosinic
olycytidylic acid (Poly I:C) stimulation.
METHODS:
A total of 11 International Consensus Criteria defined CFS/ME participants (40.42 ± 10.31), 9 World Health Organisation defined systemic mastocytosis (SM) participants (47.00 ± 10.37) and 12 healthy controls (HC) (36.36 ± 9.88) were included. Following autoMACS magnetic separation, CD117+/Lin-MCPs were stimulated with Poly I:C for 24hr. MCP purity (CD117 and Lin2), maturity (CD34 and FcεRI), interaction receptors and ligands (CD154 and HLA-DR), and SM-specific (CD2 and CD25) markers were measured using flow cytometry.
RESULTS:
There was a significant decrease in HLA-DR+/CD154- expression between CFS/ME and SM groups pre and post Poly I:C stimulation. There were no significant differences in maturity MCPs, CD154, and CD2/CD25 expression between groups pre and post Poly I:C stimulation.
CONCLUSION:
This pilot investigation provides a novel methodology to characterise MCPs in a rapid, inexpensive and less invasive fashion. We report a significant decrease in HLA-DR+/CD154- expression between CFS/ME and SM participants, and an observed increase in HLA-DR-/CD154+ expression post Poly I:C stimulation in CFS/ME participants. Peripheral MCPs may be present in CFS/ME pathophysiology, however further investigation is required to determine their immunological role.
PMID: 29223146
DOI:
10.12932/AP-200517-0086
--
Asian Pac J Allergy Immunol.2017 Jun;35(2):75-81. doi: 10.12932/AP0771.
Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients.
Nguyen T1,2,
Johnston S1,2,
Chacko A1,2,
Gibson D1,2,
Cepon J1,2,
Smith P1,2,
Staines D1,2,
Marshall-Gradisnik S1,2.
Author information
Abstract
BACKGROUND:
Mast cells (MCs) mediate inflammation through neuropeptides and cytokines, along with histamine and reactive oxygen species (ROS). Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is an illness characterized by an unexplained disabling fatigue with multiple physiological impairments as well as dysregulated cytokine profiles.
OBJECTIVE:
To determine mast cell phenotypes in isolated human PBMCs, in healthy controls and in CFS/ME patients. Second, determine receptor expression of RAGE and its ligand high mobility group box 1 protein (HMGB1).
METHOD:
Moderately severe CFS/ME patients (n=12, mean age 39.25 ± SD3.52 years), severe CFS/ME patients (n=6, mean age 43.00 ± SD4.02 years) and healthy controls (n=13, mean age 42.69 ± SD3.87 years) were included in this study. CFS/ME patients were classified according to the 2011 International Consensus Criteria. LSRFortessa X-20 Flow cytometry was used for the identification of phenotypic peripheral mast cell population in PBMCs using an exclusion marker Lin2 cocktail (anti-CD3, anti-CD14, anti-CD19, anti-CD20 and anti-CD56) and inclusion markers (CD117, CD34, FCεRI, chymase, HLA-DR and CD154) following comparative investigation. HMGB1 and soluble RAGE expression in plasma was measured by sandwich ELISA assay.
RESULTS:
There was a significant increase in CD117⁺CD34⁺FCεRI-chymase- mast cell populations in moderate and severe CFS/ME patients compared with healthy controls. There was a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cell populations in the severe CFS/ME compared with healthy controls and moderate CFS/ME. There were no significant differences between groups for HMGB1 and sRAGE.
CONCLUSIONS:
This preliminary study investigates mast cell phenotypes from PBMCs in healthy controls. We report significant increase of naïve MCs in moderate and severe CFS/ME patients compared with healthy controls. Moreover, a significant increase in CD40 ligand and MHC-II receptors on differentiated mast cells in severe CFS/ME patients. Peripheral MCs may be present in CFS/ME pathology however, further investigation to determine their role is required.
PMID: 27362406
DOI:
10.12932/AP0711
