ABSTRACT
Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells correlates with unfavorable prognosis, suggesting that CD44 variant molecules are involved in the disease process. In this study, the presence of CD44v on B cell lines from different stages of development was analyzed by flow cytometry and a role in adhesion to stromal cells from different tissues was evaluated in in vitro binding assays. CD44v3, v6 and v9 isoforms were exclusively expressed on plasma cell lines and CD44v9 expression correlated with IL-6-dependent plasma cell growth. Binding studies using CD44 isoform- specific reagents showed that CD44v6 and CD44v9 were involved in binding to bone marrow stromal cells, but not to in vitro synthesized ECM or hyaluronic acid. CD44v9-mediated plasma cell binding resulted in a significant induction of IL-6 secretion by bone marrow stromal cells. Large differences in quantitative plasma cell binding to stromal cells from different tissues were observed. These, however, could not be related to a differential use of CD44v in these binding processes. The role of CD44v9 in adhesion induced IL-6 secretion and its preferential expression on IL-6-dependent plasma cell lines may explain the previously observed correlation between CD44v9 expression and adverse prognosis in multiple myeloma.
Subject(s)
Antigens, Neoplasm/physiology , B-Lymphocytes/cytology , Bone Marrow Cells/cytology , Glycoproteins/physiology , Hyaluronan Receptors/physiology , Multiple Myeloma/pathology , Neoplastic Stem Cells/cytology , Plasma Cells/cytology , Protein Isoforms/physiology , Stromal Cells/cytology , Adult , Antibodies, Monoclonal/pharmacology , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , B-Lymphocytes/metabolism , Bone Marrow Cells/metabolism , Cell Adhesion , Child , Exons/genetics , Extracellular Matrix/metabolism , Glycoproteins/genetics , Glycoproteins/immunology , Humans , Hyaluronan Receptors/genetics , Hyaluronan Receptors/immunology , Hyaluronic Acid/metabolism , Interleukin-6/metabolism , Multiple Myeloma/mortality , Neoplastic Stem Cells/metabolism , Organ Specificity , Plasma Cells/metabolism , Prognosis , Protein Isoforms/genetics , Protein Isoforms/immunology , Recombinant Fusion Proteins/physiology , Stromal Cells/metabolismABSTRACT
To ensure prolonged survival, dogs with cyclic neutropenia should be protected against bacterial infection of exogenous or endogenous origin, particularly during the neutropenic episodes. One of the methods available to minimize the risk of infection in these dogs, is selective decontamination of the gastrointestinal tract by using antibiotics and/or chemotherapeutic agents, in conjunction with housing in a laminar-flow cabinet. Two pregnant bitches, some of the offspring of which were expected to be homozygous for the cyclic neutropenia allele, were decontaminated with nalidixic acid. Fourteen days after initiation of the antibacterial treatment, the two dogs died. Jaundice and seizures had been apparent in both animals prior to death. Histopathological examination revealed changes primarily in the liver, which were consistent with toxic hepatic necrosis and were characterized by severe centrilobular haemorrhage and disappearance of hepatocytes. Multiple haemorrhages were observed in other organs. Further clinical investigation in two other dogs strongly suggested that nalidixic acid was the cause of death in the two pregnant bitches.
