title: Macrophage migration inhibitory factor is an endogenous regulator of stress-induced extramedullary erythropoiesis.
abstract: Macrophage migration inhibitory factor is a well-known proinflammatory cytokine that is released during systemic stress response. Although MIF can affect erythrocyte production, the role of this cytokine in stress-induced erythropoiesis is completely unknown. To extend our previous findings showing that chronic psychological stress stimulates extramedullary erythropoiesis, here we examined whether MIF is involved in the control of stress-induced erythropoietic response. Adult male C57BL/6 wild-type (WT) and MIF-KO (knock-out) mice were subjected to 2-h daily restraint stress for either 7 or 14 consecutive days. The number of erythroid progenitors and CD71/Ter119 profile of erythroid precursors were analyzed in the bone marrow and spleen. Additionally, MIF protein expression was assessed in WT mice. Our results demonstrated that chronic restraint stress enhanced the number of both erythroid progenitors and precursors in the spleen. Stress-induced increase in the number of splenic late erythroid progenitors as well as in the percentage of CD71(+)Ter119(+)-double-positive precursors was significantly more pronounced in MIF-KO mice compared to WT animals. Furthermore, repeatedly stressed WT animals demonstrated an augmented MIF expression in the spleen. Unlike the spleen, the bone marrow of chronically stressed WT mice exhibited less prominent changes in erythropoietic stress response and no significant alteration in MIF expression. In addition, MIF deficiency did not influence the bone marrow erythropoiesis in stressed animals. These findings suggest that MIF regulates extramedullary erythropoiesis by inhibiting an overexpansion of splenic immature erythroid cells during chronic stress and indicate a novel role for this cytokine under chronic stress conditions.
authors.affiliation: Department of Neuroendocrinology, Institute for Medical Research, University of Belgrade, Dr Subotića 4, PO Box 39, 11129, Belgrade 102, Serbia. sanja.vignjevic@imi.bg.ac.rs.
authors.forename: Sanja
authors.initials: S
authors.lastname: Vignjević Petrinović
authors.affiliation: Department of Neuroendocrinology, Institute for Medical Research, University of Belgrade, Dr Subotića 4, PO Box 39, 11129, Belgrade 102, Serbia.
authors.forename: Mirela
authors.initials: M
authors.lastname: Budeč
authors.affiliation: Department of Immunology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Marković
authors.affiliation: Clinic of Hematology, Clinical Center of Serbia, Medical Faculty University of Belgrade, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Gotić
authors.affiliation: Department of Neuroendocrinology, Institute for Medical Research, University of Belgrade, Dr Subotića 4, PO Box 39, 11129, Belgrade 102, Serbia.
authors.forename: Olivera
authors.initials: O
authors.lastname: Mitrović Ajtić
authors.affiliation: Department of Experimental Hematology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Slavko
authors.initials: S
authors.lastname: Mojsilović
authors.affiliation: Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
authors.forename: Stanislava
authors.initials: S
authors.lastname: Stošić-Grujičić
authors.affiliation: Department of Cardiovascular Physiology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Milan
authors.initials: M
authors.lastname: Ivanov
authors.affiliation: Department of Experimental Hematology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Jovčić
authors.affiliation: Department of Experimental Hematology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladan
authors.initials: V
authors.lastname: Čokić
mesh_terms: D000818:Animals; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism*; D004920:Erythropoiesis; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013312:Stress, Physiological
chemical_list: D008263:Macrophage Migration-Inhibitory Factors
keywords: Bone marrow; Erythropoiesis; MIF; Spleen; Stress