Transferrins.
The period of transferrin discovery is worthy of a legendary book of its own. I limit myself here to summing up over 25 years of hard work and experiments that, starting with an idea I had for the necessary presence of molecules in bone marrow for the purpose of endogenous control of haematopoietic proliferation. This led, through an endless series of transplants, to the discovery of an element that I named Marrow Regulating Factor (MRF) in suspension cultures of bone marrow, When added to donor marrow from a different and genetically incompatible strain, this element brought about the so-called chimerism process in the immunosuppressed recipient, i.e., the marrow from the genetically incompatible strain was accepted. This extraordinary observation led me to believe that the MRF contained molecules from the donor that would bring about haematopoietic chimerism in an incompatible recipient. After years of work with the Choay Institute in Paris and then with the SCLAVO in Siena, I discovered that the molecules transferring the donor genes to the recipient were transferrins!
This sensation discovery was communicated by publications as a result, Therefore, transferrins are not just iron carriers, but they also contain markers of our own personal genes. This enormous discovery, which took 30 years of work at immense expense, was blocked in 2000 on the day before clinical use in Seattle (USA) by Italian Minister Sirchia, who refused to grant the required support with his memorable phrase: “I don’t believe in natural molecules”. Nothing more needs to be said, as it marks an umpteenth disgraceful Italian tragedy. The work, on the brink of enforcement by the Ministry for Health, was tragically halted in 2000.
Summary of scientific references:
- Pierpaoli W. and Maestroni G.
A new pre-irradiation conditioning regimen which protects against radiation injury and facilitates engraftment of xenogeneic bone marrow.
Scand. J. Haematol. 22, 165-172, 1979. - Pierpaoli W. and Maestroni G.
Prevention of graft-versus-host disease and induction of chimerism in lethally irradiated mice reconstituted with rat bone marrow.
J. Clin. and Lab. Immunol. 2, 125-132, 1979. - Pierpaoli W. and Maestroni G.
Induction of enduring allogeneic bone marrow chimerism in rabbits via soluble marrow-derived components.
Immunol. Let. 1, 255-258, 1980. - Pierpaoli W., Maestroni G. and Sache E.
Enduring allogeneic marrow engraftment via nonspecific bone marrow-derived regulating factors (MRF).
Cell. Immunol. 57, 219-228, 1981. - Pierpaoli W. and Maestroni G.
Enduring allogeneic and xenogeneic hemopoietic engraftment via marrow-derived regulating factors (MRF). In: Tolerance in Bone Marrow and Organ Transplantation.
(Edited by S. Slavin) pp 403-414. Elsevier, Amsterdam, 1984. - Pierpaoli W.
Immunoregulatory and morphostatic function of bone marrow-derived factors. In: Neural Modulation of Immunity.
(Edited by R. Guillemin, M. Cohn and T. Melnechuk) pp 205-220. Raven Press, New York, 1985. - Pierpaoli W., Kellerhals R., Buehler A. and Sache, E.
Experimental manipulations and marrow- derived factors which affect the outcome of bone marrow transplantation across the H-2 barrier in lethally irradiated mice.
J. Clin. Lab Immunol. 16, 115-124, 1985. - Pierpaoli W., Balakrishnan J., Maestroni G., Sache E. and Choay J.
Bone marrow: a “morphostatic brain” for control of normal and neoplastic growth. Experimental evidence.
Ann. N.Y. Acad. Sci. 521, 300-311, 1988. - Deeg H.J., Pierpaoli W., Arrighi S. Seidel K., Graham T., Huss R. Yu C., Myerson D., Schuening F. and Storb R.
Facilitation of DLA-incompatible marrow grafts by donor-derived transferrin?
Transplant Immunol. 4, 113-116, 1996. - Pierpaoli W., Lesnikov V.A., Lesnikova M.P., Arrighi S. and Bardotti A.
Specific xenogeneic (human) tolerance in immunosuppressed mice by combined donor-derived human transferrin and antigens.
Transpl. Proc. 28, 711-712, 1996. - Pierpaoli W., Lesnikov V.A., Lesnikova M.P. and Arrighi S.
Donor-derived plasma transferrin facilitates the engraftment of xenogeneic (rat) bone marrow in irradiated mice.
Bone Marrow Transplantation 18, 203-207, 1996. - Pierpaoli W.
Overcoming the histocompatibility barrier. Transferrins as carriers and modulators of immunogenic identity.
Cell Transpl. 7, 541-548, 1998. - Pierpaoli W., Bulian D. and Arrighi S.
Transferrin treatment corrects aging-related immunologic and hormonal decay in old mice.
Exp. Gerontol. 35, 401-408, 2000.