Source and hormone-dependence of GLx-gp70 in mouse serum

Abstract

The gp70 family of glycoproteins is distinguished by the role of these molecules as constituents of C-type viral envelopes and also as Mendelian cellular constituents expressed independently of virus production. The source of G(IX)-gp70 in the serum of 129 strain mice, which are not overt producers of virus, could not be traced to any organ or tissue that is known to be G(IX)-positive by serological tests. Hematopoietic tissues were excluded as source of serum G(IX)-gp70 by tests with reciprocal radiation chimeras made from 129 and 129-G(IX)(-) donors and recipients. Thymus and spleen were excluded because excision of these organs did not affect levels of G(IX)-gp70 in the serum. The serum of young adult 129 males contains roughly four times as much G(IX)-gp70 as adult 129 females and the levels rise in both sexes with increasing age. Castration of 129 males reduced the level of serum G(IX)-gp70 to that of females, and the level was fully restored by testosterone. Thus the epididymis and seminal fluid, though rich in G(IX)-gp70, do not contribute significant amounts of G(IX)-gp70 to the serum. The level of G(IX)-gp70 in the serum of testosterone-treated females, though more than double that of untreated females, did not reach the level of normal males, under the conditions tested. This may signify that G(IX)-gp70 production by males is subject to imprinting by testosterone in early life. Evidently the main source of serum G(IX)-gp70 is a tissue or organ that is common to males and females, is directly or indirectly responsive to testosterone, and has not so far been identified serologically as G(IX)- positive.

Emerging roles of TLR7 and TLR9 in murine SLE

“…Indeed, gp70 is a constituent of the surface of various epithelia and of thymocyte and mature peripheral lymphocyte cell membranes, and shares immunological and biochemical properties with the thymocyte differentiation antigen GIX [82][83][84][85][86]. It has previously been demonstrated that lymphoid cells are not a major source for serum retroviral gp70 because neither thymectomy nor splenectomy affected serum levels of gp70 [87]. Rather, serum gp70 behaves like an acute phase protein and is secreted by hepatic cells into the circulating blood [88,89].…”

Dissection of Genetic Mechanisms Governing the Expression of Serum Retroviral gp70 Implicated in Murine Lupus Nephritis

“…Indeed, gp70 is a constituent of the surface of various epithelia and of thymocyte and mature peripheral lymphocyte cell membranes, and shares immunological and biochemical properties with the thymocyte differentiation antigen GIX (11–15). It has previously been demonstrated that lymphoid cells are not a major source for serum retroviral gp70, because neither thymectomy nor splenectomy affected serum levels of gp70 (16). Rather, serum gp70 behaves as an acute phase protein and is secreted by hepatic cells into the circulating blood (17, 18).…”

Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice.

“…Increased levels of polyclonal antibody production obs~'rved in all SLEprone mice did not correlate with serum levels of gp70 (34), and gp70 concentrations remained unchanged throughout the course of disease despite the progression of autoimmune disease (12). Further, neither thymectomy, splenectomy, nor exchange of hematopoietic tissues between 129-Gix + and 129-Gix-mice changed levels of serum gpT0 in either strain (21). Finally, our recent study showed that the enhancement of serum gp70 expression by LPS was independent of the activation of B lymphocytes and of the presence of T lymphocytes (22; and I. Hara, S. Izui, and F. J. Dixon, manuscript in preparation).…”

“…Additionally, like many other serum glycoproteins (24, 35.36), gp70 may be synthesized by hepatic cells. In fact, the dependence of serum gp70 concentrations on the male sex hormone, testosterone (21), supports this possibility, because the liver is a known source of several proteins whose serum concentrations depend markedly on the host's sex (37). More directly, our preliminary studies demonstrated that the injection of LPS greatly elevated the amounts of gp70 recovered only from the liver with a parallel increase in serum gp70 (I. Hara, S. Izui, and F. J. Dixon, manuscript in preparation).…”