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.