Effect of eosinophil-degranulating estrogens on spleen eosinophils and white pulp/red pulp ratio

Abstract

A role for eosinophils in the immune reaction has not been yet established. Considering that these leukocytes accumulate in lymphoid organs under glucocorticoid stimulation, we explored the possibility that they participate in the depression of immune reactions induced by these hormones and that they degranulate to exert this action. In this context, we investigated the dose effect of three estrogens on the number and degranulation of spleen red pulp eosinophils and on the percentage of spleen cross sectional area comprising white pulp. Estradiol-17 beta or 4 (OH) estradiol-17 beta increased red pulp eosinophils at low doses: 2 (OH) estradiol-17 beta increased them at a very high dose. The three estrogens degranulated the spleen eosinophils and decreased the lymphocyte containing spleen white pulp. We propose that the decrease in white pulp is a response mediated by agents released from degranulating eosinophils under the action of estrogen. Consequently, both estrogen-induced eosinophil degranulation and estrogen-induced increase in red pulp eosinophil numbers are conditions contributing to a decrease in white pulp volume. All above evidence supports the hypothesis that eosinophils are involved in immunoregulation by diminishing the number of lymphocytes contained in lymphoid organs.

Effect of Subacute Exposure to Lead and Estrogen on Immature Pre-Weaning Rat Leukocytes

“…Eosinophils were proposed to play a role in glucocorticoid-induced immune regulation in the rat (Tchernitchin et al 1990). In fact, they migrate to the spleen, thymus and lymph nodes under stimulation by glucocorticoid hormones (Sabag et al 1978), where they release the eosinophil cationic protein (ECP) and eosinophil protein X (EPX) (Tchernitchin et al 1990), known to inhibit the proliferation of T lymphocytes in a non-cytotoxic way (Peterson et al 1986).…”

“…In fact, they migrate to the spleen, thymus and lymph nodes under stimulation by glucocorticoid hormones (Sabag et al 1978), where they release the eosinophil cationic protein (ECP) and eosinophil protein X (EPX) (Tchernitchin et al 1990), known to inhibit the proliferation of T lymphocytes in a non-cytotoxic way (Peterson et al 1986). Further work is necessary to explore the possibility that leadinduced eosinophil degranulation interferes with glucocorticoid-induced immune regulation, and to investigate whether these findings do apply to humans.…”

“…(a) Lead decreases plasma levels (Mahaffey et al 1982) and action (Long & Rosen 1994) of 1,25 dihydroxyvitamin D 3 , which stimulates macrophage differentiation and plays a role in monocytes and activated lymphocytes due to the presence, in these cells, of vitamin D receptors (Thomasset 1994). (b) Lead induces a stress reaction (Nation et al 1987), that is characterized by the synthesis of specific stress proteins (Shelton et al 1986), an alteration of the hormonal response to stress (Chowdhury et al 1986;Agrawal & Chansouria 1989) and an increase in plasma levels of glucocorticoids (Vyskocil et al 1991); the latter is known to inhibit several immune mechanisms (Cupps & Fauci 1982;Tchernitchin et al 1990). (c) Lead induced alteration at the hypothalamus-pituitary level may also interfere with immune responses.…”

“…Lymphocytes possess glucocorticoid and sex steroid receptors, their ligands were suggested to play a role in immune regulation (Cupps & Fauci 1982;Danel et al 1983). Eosinophils were also implicated in glucocorticoid-induced immune regulation in lymphoid organs (Tchernitchin et al 1989(Tchernitchin et al , 1990. In addition to the uterine eosinophils (Tchernitchin et al 1989), endometrial intraepithelial lymphocytes (Kamat & Isaacson 1987) were implicated in the inhibition of the immune response to implantation.…”

“…Eosinophils display two kind of estrogen receptors: the high affinity membrane receptor is a cell adhesion molecule involved in estrogen-induced uterine vascular endothelium recognition by the eosinophils (Tchernitchin et al 1985b); the second, lower affinity, estrogen receptor is involved in eosinophil activation and degranulation within the uterine extravascular space (Tchernitchin et al 1985b(Tchernitchin et al , 1989. The recognition of the uterus by the eosinophils, their migration through endothelial lining, their accumulation in the uterine stroma and subsequent activation and degranulation are required for the development of the eosinophil-mediated responses to estrogen (Tchernitchin et al 1989(Tchernitchin et al , 1990. The finding that these responses develop even in the absence of estrogen, provided eosinophils have migrated to the uterus, suggests that agents released from degranulating eosinophils, and not estrogen itself, are involved in their development (see Tchemitchin et al 1989 for a review).…”