Inhibiteur de rejet de greffe alpha2-macroglobulin in burn injury: a suppressive activity on complement.

A subform of alpha2-macroglobulin, (inhibiteur de rejet de greffe (IRG), present at a low rate in healthy rat, increased with rate-related suppressive activity on complement during inflammatory processes. In human serum, a molecule with such properties was described. Serum and blister IRG from burn patients belonging to a selected population was purified under gentle conditions. Serum IRG increased quickly within the first day after hospitalization and continued to increase until day 6. Although absent in whole serum, the rate-related activity of IRG varied according to the surface area and the degree of burns. A rate-related activity was also revealed in whole blister fluid and in purified blister IRG. We report a new site and a new suppressive activity of IRG in its native form from serum and blister fluid during inflammatory processes of burned patients. The suppressive activity of IRG on complement is discussed, and it appears to play a role in the development of inflammatory processes.

Maternal alloimmunization in rat pregnancy: in vivo and in vitro studies of T-cell-dependent immunity to mating and third party alloantigens.

Rat pregnancy, experimental pseudopregnancy, and experimental decidua induction promote skin allograft survival of paternal and unrelated skin donors by specific and nonspecific mechanisms. Experimental pseudopregnant females were given allogeneic cells by two routes: intraperitoneal (IP) and in utero (IU). The females injected by the IU route, with allosensitized spleen cells, tolerated paternal skin allografts (average 26 days) better than those from other experimental groups and even from allopregnant females bearing a paternal allograft. The orthotopic immunization by the IU route, as shown by an enhancing effect of in utero culture medium injection, seemed important. In vitro studies revealed that the ability of subscapular lymph node (SCLN) cells draining the allograft to destroy Wistar/Furth (W/Fu) target cells decreases markedly in parallel with prolongation of skin allograft survival. Suppression of lymphocyte-mediated cytotoxicity against W/Fu target cells exceeded 70% when SCLN cells were used as responder cells. We propose that maternal T-cell immunization (via in utero) against fetal antigens occurs in pregnancy and plays a role in maintaining fetal tolerance, while specific cell-mediated cytotoxicity is impaired. Both specific and nonspecific local factors may promote such an enhancement of allograft survival.

Evidence for an alpha 2-macroglobulin with complement-inhibiting activity in rat serum.

alpha 2-Macroglobulin (alpha 2M) was purified both from the serum of male rats developing an acute turpentine-induced inflammatory reaction where its concentration is greatly increased (3-4 mg/ml) and from the serum of healthy males where it is present at low levels (15-30 micrograms/ml). A three-step purification procedure involving gel filtration, anion exchange chromatography on DEAE cellulose and negative immunoaffinity was used. A pure native alpha 2M, as assessed by biochemical and immunological tests, was obtained. This alpha 2M differed from other subforms in terms of its electric charge and its complement-inhibiting activity in a complement-dependent immune haemolysis test. Moreover, this inhibitory activity was not affected by complexing with trypsin or modification by interaction with methylamine showing that this newly described property is not linked to the well known antiproteinase function of alpha 2M.

Characterization of one alpha 2-macroglobulin with anticomplementary activity from pregnant women.

In 15 pregnant women during the third term of pregnancy, the immunomodulatory property of alpha 2-macroglobulin (alpha 2M) was initially detected by measuring the inhibitory effect on immune complement-dependent haemolysis of serum alpha 2M fractions obtained by gel filtration. By a two-step chromatography procedure consisting of gel filtration followed by anion-exchange chromatography, different sub-forms of alpha 2M in serum were separated. Amongst them, it was shown that the inhibition of complement activity was almost exclusively linked to one particular subform. Additional studies revealed that the observed effect was not due to proteases bound to alpha 2M during clotting since, by using protease-specific inhibitors, no change was observed in complement inhibition. This subform, though present at very low levels in control sera, appeared in strikingly increased amounts during the third trimester of pregnancy (35 mg/l) and comprised between 3 and 5% of the total alpha 2M. Results show that the increase of alpha 2M anticomplementary activity is linked to the increase in alpha 2M levels in serum.

[Preliminary study in female rats of the immunoregulatory effect of estradiol, progesterone and pituitary prolactin on natural killer-like cell mediated cytotoxic activity]. / Etude préliminaire chez la ratte de l'effet immuno-modulateur de l'oestradiol, de la progestérone et de la prolactine hypophysaire sur l'activité cytotoxique à médiation cellulaire "natural killing-like".

A spontaneous non-immune natural killing-like cytotoxic activity is induced in cyclic non mated virgin F/344 females by progesterone + oestradiol or progesterone alone treatment after bilateral ovariectomy. Many indications attribute this cytotoxic response to the absence of the mating stimulated pituitary prolactin release which normally rescues the corpora lutea from regression, and brings about the necessary progesterone for pregnancy or pseudopregnancy.

Rat pregnancy induces two suppressor cell activities.

Pregnancy in rat is able to stimulate two suppressor cell activities. One is specific to the paternal histocompatibility antigens and it resides in the T-lymphocyte population. The second is nonspecific and is of non-T nature. The use of various methods for pseudopregnancy and deciduoma installation has allowed the demonstration of two inducing circuits: (a) the presence of fertilized ova in the female genital tract and (b) the progestation hormonal status.

Rat pregnancy immunoregulatory circuits are progestation hormonal status, decidual tissue, embryo-trophoblast and late pregnancy changes dependent.

We have tested the spleen cells of rats for their reactivity to mating and unrelated (third party) strain alloantigens during pregnancy, pseudopregnancy, and traumatic deciduoma installation. By cytotoxic T-lymphocyte assays, after 7-day one-way mixed lymphocyte cultures (MLC), we detected the presence of many immunoregulatory circuits among rat pregnancy and postpartum. They are progestation hormonal status, decidual tissue, embryo-trophoblast, late-pregnancy-parturition-associated changes, and lactation-hormonal-status dependent.

Antagonistic maternal immune reactions (rejection and facilitation) to the embryo in the urodele amphibian Salamandra salamandra lin.

In vitro assays have been employed to demonstrate that pregnant salamanders mount an immune reaction against their embryos. Maternal spleen cells kill up to 85% of dissociated embryonic epidermal cells during a 48 h incubation period. The degree of killing depends upon the ratio of maternal to embryonic cells and on the number of embryos borne by the mother. The cytotoxicity shows considerable specificity for the embryos of a given mother although a weak degree of killing can occur with embryos from other mothers, presumably due to some form of cross-reactivity. The effect is inhibited by the addition of maternal serum to the cultures. The degree of protection is also a function of the number of embryos borne by the mother. Pre-incubation experiments indicate that the maternal serum has a protective action on the embryonic cells which is largely specific for the female's own embryos (and suggested to be antibody in nature) and an inhibitory action on the maternal spleen cells which occurs also with spleen cells of other females (and suggested to be either an immune complex or a nonimmunological substances). An increase in beta protein peaks is seen following electrophoresis of sera from pregnant (and also allografted) salamanders. These findings indicate that the pregnant salamander mounts a double immune reaction against her embryos, an aggressive (rejection) reaction and a protective (facilitation) reaction.