Potentiation of erythroid abnormalities following macrophage depletion in aged rats.
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.
Lisa Giuliani
Anna
A
Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy. a.giuliani@unife.it
Graldi
Giuseppe
G
Veronesi
Massimo
M
Lorenzini
Franco
F
Gandini
Gloria
G
Unis
Lorenza
L
Previato
Antonio
A
Wiener
Edith
E
Wickramasinghe
Sunitha N
SN
Berti
Gilberto
G
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
D004164:Diphosphonates; C118184:LE-Cl2MDP; D008697:Methane