Myeloproliferation in long-term plasmacytoma-regressor mice.
MOPC-315 plasmacytoma-bearing BALB/c mice were treated with high doses of melphalan, causing a permanent and complete regression of the tumor. In the present study we analyzed plasmacytoma-regressor mice (PRM) 3-6 months after plasmacytoma regression. A second group of otherwise untreated normal mice was treated with melphalan (M--control group). A third group of mice remained untreated and served as an age- and sex-matched control group. PRM were cachectic and had an increased mortality rate compared to the M and the C control groups. Histopathological examination indicated that the spleen of PRM showed pronounced abnormalities, primarily in the red pulp. These abnormalities consisted of extramedullary hematopoiesis and myeloid-granulocytic hyperplasia. Spleens of M mice showed similar abnormalities but to a much lesser extent. Flow cytometric analysis of cellular surface markers of PRM splenocytes indicated a high number of large MAC-I- and GR-I-positive cells compared to splenocytes of M or C controls. These large cells also expressed Fc tau receptors (Fc tau RII), stained positively with non-specific esterase and adhered to plastic dishes; a certain percentage expressed MAC-2 and MAC-3 antigens. A quantitative suppression of CD4+ T cells and of B cells was also shown. Circulating levels of TNF were higher in PRM than in M or C mice. The capacity of splenocytes from PRM to secrete factors that stimulated CFU-GM colony formation in soft agar by bone-marrow cells from normal mice was significantly up-regulated compared to that of splenocytes from M or C mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Sagi-Assif
O
O
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel.
Douer
D
D
Shaked
N
N
Russell
S W
SW
Witz
I P
IP
D000818:Animals; D001854:Bone Marrow Cells; D002100:Cachexia / Q000209:etiology / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D003115:Colony-Stimulating Factors / Q000096:biosynthesis / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D006098:Granulocytes / Q000473:pathology*; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010641:Phenotype; D010954:Plasmacytoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013163:Splenomegaly / Q000473:pathology; D013997:Time Factors
D003115:Colony-Stimulating Factors; D016207:Cytokines; D008558:Melphalan