Elsevier

Medical Hypotheses

Volume 94, September 2016, Pages 126-131
Medical Hypotheses

Is chondroitin sulfate responsible for the biological effects attributed to the GC protein-derived Macrophage Activating Factor (GcMAF)?

https://doi.org/10.1016/j.mehy.2016.07.012Get rights and content

Abstract

We hypothesize that a plasma glycosaminoglycan, chondroitin sulfate, may be responsible for the biological and clinical effects attributed to the Gc protein-derived Macrophage Activating Factor (GcMAF), a protein that is extracted from human blood. Thus, Gc protein binds chondroitin sulfate on the cell surface and such an interaction may occur also in blood, colostrum and milk. This interpretation would solve the inconsistencies encountered in explaining the effects of GcMAF in vitro and in vivo. According to our model, the Gc protein or the GcMAF bind to chondroitin sulfate both on the cell surface and in bodily fluids, and the resulting multimolecular complexes, under the form of oligomers trigger a transmembrane signal or, alternatively, are internalized and convey the signal directly to the nucleus thus eliciting the diverse biological effects observed for both GcMAF and chondroitin sulfate.

Section snippets

Introduction: A brief history of GcMAF research and controversies

The group-specific component (Gc) protein-derived Macrophage Activating Factor (GcMAF), a protein that is extracted from human blood, has received a great deal of attention in the past few years because of its proposed therapeutic use in the immunotherapy of cancer and other diseases ranging from autism and AIDS to multiple sclerosis and lupus [1], [2], [3], [4], [5], [6], [7], [8], [9], [10].

GcMAF derives from the Gc protein, also know as vitamin D binding protein, a carrier protein highly

Inconsistencies in the current hypothesis concerning the interpretation of the observed results

Despite the encouraging evidences concerning the effectiveness of human blood-derived GcMAF, there are significant inconsistencies at the molecular and clinical level that force us to question the interpretation of the results reported above, which include our own results, and to propose a novel hypothesis that may help solving such inconsistencies.

A novel hypothesis concerning the interpretation of the results reported for GcMAF

In order to solve the inconsistencies described above, we reconsidered the molecular structure of GcMAF and its mode of action. In fact, despite the wealth of information on this molecule, the details of its interaction with specific, or non-specific, cellular receptors are still missing. It is worth noticing that a receptor for GcMAF has never been described in molecular detail.

However, several years ago, it was demonstrated that the Gc protein binds to a variety of cells that include cells of

A molecular model of interaction between chondroitin sulfate and the Gc protein

It can be hypothesized that the interaction between the Gc protein and chondroitin sulfate occurs both at the level of the plasma membrane, as demonstrated by DiMartino and Kew [37], as well as in serum, colostrum and milk. Thus, given the abundance of Gc protein and chondroitin sulfate in the same fraction of plasma, an interaction between the two circulating macromolecules appears almost certain and it is conceivable that such an interaction may confer novel biological properties to the

Implications and predictions deriving from this novel hypothesis

Our hypothesis concerning the role of chondroitin sulfate in the effects attributed to GcMAF, leads to two different implications that may be rather easily proven by future experiments:

  • 1.

    Chondroitin sulfate per se is responsible for all the biological effects attributed to GcMAF.

  • 2.

    Alternatively, it is the complex formed between the Gc protein (deglycosylated or not) and chondroitin sulfate that is responsible for the biological effects attributed to GcMAF.

Both predictions could be easily evaluated,

Conclusions

We show evidence supporting the hypothesis that a plasma glycosaminoglycan, chondroitin sulfate, may be responsible for the biological and clinical effects attributed to the GcMAF, a protein that is extracted from human blood. Thus, it is known that the precursor of GcMAF, the Gc protein, binds chondroitin sulfate on the cell surface and such an interaction may occur also in bodily fluids such as blood, colostrum and milk where both the Gc protein and chondroitin sulfate are present in

Conflict of interest

The Authors are affiliated with the company “dr. reinwald healthcare”, a private company that organizes seminars and trainings for therapists and commercializes nutritional supplements and therapy devices. None of the products or devices distributed by the company is explicitly mentioned in this article and the Authors have not received financial compensation for writing this article.

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