Red Blood Cell Deformability, Vasoactive Mediators, and Adhesion, McMahon, 2019

[SNT Gatchaman]

Red Blood Cell Deformability, Vasoactive Mediators, and Adhesion
Timothy J. McMahon
Open Access

Healthy red blood cells (RBCs) deform readily in response to shear stress in the circulation, facilitating their efficient passage through capillaries. RBCs also export vasoactive mediators in response to deformation and other physiological and pathological stimuli.

Deoxygenation of RBC hemoglobin leads to the export of vasodilator and antiadhesive S-nitrosothiols (SNOs) and adenosine triphosphate (ATP) in parallel with oxygen transport in the respiratory cycle. Together, these mediated responses to shear stress and oxygen offloading promote the efficient flow of blood cells and in turn optimize oxygen delivery.

In diseases including sickle cell anemia and conditions including conventional blood banking, these adaptive functions may be compromised as a result, for example, of limited RBC deformability, impaired mediator formation, or dysfunctional mediator export. Ongoing work, including single cell approaches, is examining relevant mechanisms and remedies in health and disease.

 

[SNT Gatchaman]

Deformation of RBCs is necessary for their flow and thus for cellular respiration, and not only promotes the physical passage of RBCs through microvessels, but also leads to the export of vasoactive and antiadhesive mediators, further optimizing flow as a function of need.

These paracrine responses are analogous to the metabolically responsive and allosterically regulated export of vasoactive and antiadhesive ATP or SNO in response to RBC Hb deoxygenation.

The deformation/mediator export/antiadhesive pathway is disturbed in pathology according to mechanisms that are still being identified. Primary or secondary defects in RBC deformability have the dual effect of directly impairing the ability of the RBC to flow freely through capillaries, and blunting the release of vasoactive mediators necessary for vasoregulation.

Meanwhile, approaches to correcting such lesions or exploiting these delivery routes for broader therapeutic gain are being tested, informed by growing recognition of the molecular determinants of RBC mediator formation, release, and activity within the RBC and beyond.

See also
The Deformability of Red Blood Cells in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - Thesis: Brendan Robert Schmidt 2019
and
Review: Squeezing for Life – Properties of Red Blood Cell Deformability, 2018, Huisjes et al

 

[alex3619]

I first encountered these ideas in connection with CFS (the favoured term in the time this was going on) in the late 90s. Stanford (Open Medicine Foundation?) did some preliminary experiments in recent years and could not find the problem if I am interpreting what I recall correctly. However its possible it exists and needs very fresh blood, especially for controls. Its also possible we are doing the wrong tests. This hypothesis with regards to ME is not dead in my opinion, but its going to take groundbreaking research to demonstrate it.

Its a similar story for vasoactive regulators. I first ran into that hypothesis at around the same time.

If I recall things correctly, these ideas were first championed for CFS (not the more modern views of ME) in New Zealand and Australia respectively.