Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function

Abstract

Natural glucocorticoids (Gc) produced during stress have profound effects on the immune system. It is well known that Gc induce apoptosis in precursor T and B cells, markedly altering lymphopoiesis. However, it has been noted that marrow myeloid cells expanded both in proportion and absolute numbers in the mouse after Gc exposure. Mice were implanted with a corticosterone (CS) tablet that increased serum Gc and caused atrophied thymuses, both classic signs of activation of the stress axis. Blood neutrophil counts were elevated (4.8؋), whereas lymphocyte counts declined. Flow cytometric analysis of the marrow revealed that the phenotypic distribution of the various major classes of cells was shifted by Gc exposure. As expected, marrow lymphocyte numbers declined >40% after 3 days of exposure to Gc. Conversely, in the myeloid compartment, both monocytes and granulocytes increased in number by >40%. Further, all granulocyte developmental stages showed large increases in both total number and percentage of cells. To investigate the functional capacity of mature granulocytes from Gc-treated mice, an improved granulocyte isolation method was developed. Gc exposure had little effect on the ability of granulocytes to produce superoxide or undergo chemotaxis or phagocytose bacteria. These results indicate that Gc treatment shifts bone marrow composition and provides evidence that granulocytes and their progenitors are selectively preserved under stressful conditions without losing function.granulopoiesis ͉ lymphopoiesis

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“…However, administration of exogenous glucocorticoids has variable effects on erythropoiesis: increased Gordon 1955a, 1955b;Malgor et al 1974) or unchanged (Laakko and Fraker 2002). Glucocorticoids are also involved in expansion of all developmental stages of myeloid bone marrow cells, contributing to increased circulating neutrophil counts (Bishop et al 1968;Trottier et al 2008). In mice, injection of corticosterone at doses approximating short-term stress affects the bone marrow by decreasing lymphoid cell and increasing granulocytic precursors, without affecting erythroid or monocytic cell counts or total cellularity (Laakko and Fraker 2002).…”