 | |  | |  | |  | |  | |  | |  | |  |
| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2(3):266-279;2009.
Original Article
A novel biologic immunomodulator, HDFx, protects against lethal hemorrhage,
endotoxins and traumatic injury: potential relevance to emerging diseases
Burton M. Altura, Asefa Gebrewold, Anthony Carella
Department of Physiology and Pharmacology, Department of Medicine, and The Center for Cardiovascular & Muscle Biology, State
University of New York, Downstate Medical Center, Brooklyn, New York 11203; Bio-Defense Systems, Inc, Rockville Centre 11570
Received September 3, 2009; accepted October 8, 2009; available online October 15, 2009
Abstract: For more than 125 years, it has been known that the RES, macrophages and the innate immune system play fundamental
roles in host defense against pathogenic infections, trauma ,hemorrhage, and combined injuries. Some years ago,we and others
reported that the RES-macrophage system was intimately connected to resistance to these bodily stressors, among other injuries. We
tested the hypothesis that induction of tolerance (either spontaneous, RES-stimulated ,or drug-induced ) might be associated with
production of a yet-to-be- identified biologic host defense factor ,which we have termed HDFx. The results presented, herein,
demonstrate for the first time that: 1) the MW of this protein, HDFx, is approximately 35-40 KDa , larger than known defensin peptides
and much smaller than the larger MW fibronectins and complement products; 2) we describe some of HDFx’s physico-chemical
characteristics; 3) approximately 80 % of HDFx’s plasma biological activity is derived from macrophages;4) about 15-20 % of its activity
is derived from natural killer (NK ) cells; 5) polymorphonuclear leukocytes are not a source of HDFx synthesis or release; 6) known
stimulants of the RES-macrophage system (i.e., denatured human serum albumin ,triolein, and choline chloride) effect phagocytic
stimulation of macrophages and protection against endotoxins ,trauma ,and hemorrhage via synthesis and release of HDFx; 7)
adaptation to lethal trauma is dependent on the biological activity of HDFx; and 8) repeated administration of purified HDFx to rats, over
several months, does not produce any detectable pathologies. Lastly, the release of cytokines (i.e., IL-2,IL-6,IFN-gamma) from
lymphocytes, after hemorrhage and trauma, at least in rodents, appears to be dependent on the available plasma levels of HDFx. Since
it is present also in mice, guinea-pigs, and rabbits, we are tempted to speculate that HDFx could prove (if found in humans) to be
useful against potential biothreats, new emerging diseases, high –risk surgical procedures,hospital-borne infections, and burn
injuries, where the chances for superimposed bacterial infections present great risk. (IJCEM909003).
Key words: Macrophages, reticuloendothelial system, natural killer cells, leukocytes, phagocytes, lymphocyte cytokines
Full text PDF
Address all correspondence to:
Burton M. Altura , PhD
SUNY Downstate Medical Center,
Box 31, 450 Clarkson Avenue
Brooklyn, NY 11203
Tel: 718-270-2194; FAX: 718-270-3103
Email: baltura@downstate.edu
Original Article
A novel biologic immunomodulator, HDFx, protects against lethal hemorrhage,
endotoxins and traumatic injury: potential relevance to emerging diseases
Burton M. Altura, Asefa Gebrewold, Anthony Carella
Department of Physiology and Pharmacology, Department of Medicine, and The Center for Cardiovascular & Muscle Biology, State
University of New York, Downstate Medical Center, Brooklyn, New York 11203; Bio-Defense Systems, Inc, Rockville Centre 11570
Received September 3, 2009; accepted October 8, 2009; available online October 15, 2009
Abstract: For more than 125 years, it has been known that the RES, macrophages and the innate immune system play fundamental
roles in host defense against pathogenic infections, trauma ,hemorrhage, and combined injuries. Some years ago,we and others
reported that the RES-macrophage system was intimately connected to resistance to these bodily stressors, among other injuries. We
tested the hypothesis that induction of tolerance (either spontaneous, RES-stimulated ,or drug-induced ) might be associated with
production of a yet-to-be- identified biologic host defense factor ,which we have termed HDFx. The results presented, herein,
demonstrate for the first time that: 1) the MW of this protein, HDFx, is approximately 35-40 KDa , larger than known defensin peptides
and much smaller than the larger MW fibronectins and complement products; 2) we describe some of HDFx’s physico-chemical
characteristics; 3) approximately 80 % of HDFx’s plasma biological activity is derived from macrophages;4) about 15-20 % of its activity
is derived from natural killer (NK ) cells; 5) polymorphonuclear leukocytes are not a source of HDFx synthesis or release; 6) known
stimulants of the RES-macrophage system (i.e., denatured human serum albumin ,triolein, and choline chloride) effect phagocytic
stimulation of macrophages and protection against endotoxins ,trauma ,and hemorrhage via synthesis and release of HDFx; 7)
adaptation to lethal trauma is dependent on the biological activity of HDFx; and 8) repeated administration of purified HDFx to rats, over
several months, does not produce any detectable pathologies. Lastly, the release of cytokines (i.e., IL-2,IL-6,IFN-gamma) from
lymphocytes, after hemorrhage and trauma, at least in rodents, appears to be dependent on the available plasma levels of HDFx. Since
it is present also in mice, guinea-pigs, and rabbits, we are tempted to speculate that HDFx could prove (if found in humans) to be
useful against potential biothreats, new emerging diseases, high –risk surgical procedures,hospital-borne infections, and burn
injuries, where the chances for superimposed bacterial infections present great risk. (IJCEM909003).
Key words: Macrophages, reticuloendothelial system, natural killer cells, leukocytes, phagocytes, lymphocyte cytokines
Full text PDF
Address all correspondence to:
Burton M. Altura , PhD
SUNY Downstate Medical Center,
Box 31, 450 Clarkson Avenue
Brooklyn, NY 11203
Tel: 718-270-2194; FAX: 718-270-3103
Email: baltura@downstate.edu
