title: Potentiation of erythroid abnormalities following macrophage depletion in aged rats.
abstract: OBJECTIVE
  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 (Cl2MDP-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 Cl2MDP-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.
  
  
  CONCLUSIONS
  Haematological abnormalities because of Cl2MDP-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.
authors.affiliation: Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy. a.giuliani@unife.it
authors.forename: Anna
authors.initials: A
authors.lastname: Lisa Giuliani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Graldi
authors.forename: Massimo
authors.initials: M
authors.lastname: Veronesi
authors.forename: Franco
authors.initials: F
authors.lastname: Lorenzini
authors.forename: Gloria
authors.initials: G
authors.lastname: Gandini
authors.forename: Lorenza
authors.initials: L
authors.lastname: Unis
authors.forename: Antonio
authors.initials: A
authors.lastname: Previato
authors.forename: Edith
authors.initials: E
authors.lastname: Wiener
authors.forename: Sunitha N
authors.initials: SN
authors.lastname: Wickramasinghe
authors.forename: Gilberto
authors.initials: G
authors.lastname: Berti
mesh_terms: D000367:Age Factors; D000375:Aging / Q000473:pathology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D004164:Diphosphonates / Q000008:administration & dosage; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology*; D004920:Erythropoiesis / Q000187:drug effects; D005434:Flow Cytometry; D007275:Injections, Intravenous; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D008697:Methane / Q000008:administration & dosage; D018962:Phlebotomy / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: D004164:Diphosphonates; C118184:LE-Cl2MDP; D008697:Methane