Rapid changes in the lymphopoietic and granulopoietic compartments of the marrow caused by stress levels of corticosterone.
Exposure to concentrations of glucocorticoids analogous to those produced during stress, trauma and malnutrition had rapid but varying effects on the major classes of cells within the marrow. Corticosterone (CS) was given as a subdermal implant in young mice and generated 60-95 microg CS/dl of blood compared to 5-15 microg CS/dl for sham controls over a period of 36 hr. Within 24 hr CS had caused losses of 30-70% among the early pro-B, pre-B and immature B cells. The pre-B cells were virtually eliminated by 36 hr and the capacity of surviving pro- and pre-B cells to cycle was reduced by 70-80%. Interestingly, the earliest of B cells, the prepro-B cells, showed considerable resistance to CS, being reduced by only 20% at 36 hr. Thus, the pattern of survival within the B-cell compartment paralleled the expression of Bcl-2. At the 36-hr time-point there were no changes in the proportion of progenitor cells, erythroid or monocytic cells, or number of nucleated cells in the marrow. By contrast, 36 hr after exposure to CS there was an increase of 30% in the proportion and absolute number of cells in the granulocytic compartment. Chronic production of CS appears to reprogramme lymphopoiesis and myelopoiesis, perhaps to preserve the first line of immune defence at the expense of the lymphoid branch. Resistance to apoptosis and modifications in the activity of the glucocorticoid receptor and cytokines produced by stromal cells are postulated as targets for CS-driven changes.
Laakko
Tonya
T
Department of Biochemistry and Molecular Biology,Michigan State University, East Lansing, Michigan 48824-1319, USA.
Fraker
Pamela
P
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology; D001854:Bone Marrow Cells / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D002470:Cell Survival; D003345:Corticosterone / Q000502:physiology*; D019891:Leukopoiesis / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D013312:Stress, Physiological / Q000473:pathology* / Q000503:physiopathology
D019253:Proto-Oncogene Proteins c-bcl-2; D003345:Corticosterone