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Potentiation of erythroid abnormalities following macrophage depletion in aged rats
Author(s) -
Lisa Giuliani Anna,
Graldi Giuseppe,
Veronesi Massimo,
Lorenzini Franco,
Gandini Gloria,
Unis Lorenza,
Previato Antonio,
Wiener Edith,
Wickramasinghe Sunitha N.,
Berti Gilberto
Publication year - 2007
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.0902-4441.2006.t01-1-ejh3017.x
Subject(s) - spleen , phlebotomy , erythropoiesis , macrophage , medicine , bone marrow , endocrinology , ageing , reticulocyte , splenocyte , red blood cell , haematopoiesis , immunology , anemia , biology , biochemistry , stem cell , genetics , messenger rna , gene , in vitro
Objectives: The effects of prolonged macrophage depletion on haematological parameters were investigated in aged rats and compared with those in young ones. Methods: Four weekly i.v. injections of dichloromethylene diphosphonate‐containing liposomes (Cl 2 MDP‐CL) were employed to achieve a prolonged depletion of bone marrow (BM) and spleen macrophages. The number of BM macrophages was then assessed by flow cytometry, whereas the spleen clearance function was judged by the elimination of oxidised red blood cells (RBC). Haematological parameters and signs of RBC ageing (reduced MCV, increased density and augmented 4.1a/4.1b membrane protein ratio) were determined. Finally, the recovery from phlebotomy‐induced acute anaemia was investigated. Results: Following the Cl 2 MDP‐CL treatment, in comparison with young rats, the aged animals showed: (i) reduced numbers of BM macrophages; (ii) greater impairment of spleen clearance function; (iii) similar anaemic condition and signs of RBC ageing; (iv) greater increase in white blood cell (WBC) numbers (mainly neutrophils). In addition, whereas aged control rats showed a recovery from phlebotomy‐induced acute anaemia which was similar to that of the untreated young animals, in the aged‐treated rats, a significantly diminished/delayed restoration of RBC, Hb and reticulocyte to normal values was observed, accompanied by a significantly higher increase in WBC numbers than in the other groups of animals. Conclusion: Haematological abnormalities because of Cl 2 MDP‐CL‐induced macrophage depletion are potentiated in aged rats in which the BM regenerative potential of the erythroid lineage as well as the clearance function of the spleen appear compromised. Thus, in aged rats, macrophage dysfunction is likely to interfere with erythroid homeostasis particularly during haemopoietic stress.