heparitin-sulfate and Lymphoma--Non-Hodgkin

Pasteurella (P) multocida exists in a variety of animals and causes diverse infections in humans due to animal bites and scratches, usually by cats or dogs, and oral and respiratory infection. We report a case of P multocida sepsis due to a scratch from a pet cat, complicated with disseminated intravascular coagulation in a post-chemotherapy neutropenic patient with non-Hodgkin lymphoma. The patient was a febrile 79-year-old woman with disturbed consciousness and subcutaneous abscess in her right hand due to a scratch from a pet cat. She was successfully treated with empirical antibiotic therapy with cefepime and administrations of granulocyte colony-stimulating factor and danaparoid. The minimum inhibitory concentration of cefepime against the isolate from this case was <2mg/L. Although a few days are required before a diagnosis of P multocida infection can be made from a bacteriological study, the infection can be successfully treated against febrile neutropenia with empirical cefepime. In a literature review, 7 cases, including ours, with hematological malignancies complicated with P multocida infection were identified and we summarized the clinical characteristics of these cases. These cases demonstrate the importance of the prevention of close contact between pet animals and immunocompromised hosts such as post-chemotherapy neutropenic patients.

Topics: Aged; Animals; Animals, Domestic; Anti-Bacterial Agents; Anticoagulants; Bites and Stings; Cats; Cefepime; Cephalosporins; Chondroitin Sulfates; Dermatan Sulfate; Female; Granulocyte Colony-Stimulating Factor; Heparitin Sulfate; Humans; Lymphoma, Non-Hodgkin; Neutropenia; Pasteurella Infections; Pasteurella multocida; Sepsis

Adherence of hematopoietic progenitor cells (HPCs) to stroma is an important regulatory step in megakaryocytic differentiation. However, the mechanisms through which megakaryocytic progenitors are inhibited by stroma are poorly understood. We examined the role of sulfated glycoconjugates, such as proteoglycans (PGs), on human bone marrow stroma (hBMS). To this end, PG structure was altered by desulfation or enzymatic cleavage. PGs participated in adhesion of human HPC, as desulfation resulted in about 50% decline in adhesion to hBMS. Heparan sulfate proteoglycans (HSPGs) were found to be responsible by showing about 25% decline in adhesion after pre-incubation of HPC with heparin and about 15% decline in adhesion after enzymatic removal of HSPGs from hBMS. Furthermore, PGs were involved in binding cytokines. Both desulfation and enzymatic removal of stromal HSPGs increased release of megakaryocytopoiesis-inhibiting cytokines, that is, interleukin-8 (IL-8, 1.9-fold increase) and macrophage inflammatory protein-1alpha (MIP-1alpha, 1.4-fold increase). The megakaryocytic output of HPC grown in conditioned medium of desulfated stroma was decreased to 50% of the megakaryocytic output in CM of sulfated stroma. From these studies, it can be concluded that PGs in bone marrow, in particular HSPGs, are involved in binding HPC and megakaryocytopoiesis-inhibiting cytokines. Bone marrow stromal PGs thus reduce differentiation of HPC toward megakaryocytes.

Topics: Acute Disease; Antigens, CD34; Blood Proteins; Bone Marrow; Cell Adhesion; Cell Differentiation; Cells, Cultured; Chemokine CCL3; Chemokine CCL4; Culture Media, Conditioned; Eosinophil Major Basic Protein; Hematopoietic Stem Cells; Heparitin Sulfate; Humans; Interleukin-8; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Macrophage Inflammatory Proteins; Megakaryocytes; Proteoglycans; Stromal Cells

In a human non-Hodgkin (B) lymphoma xenograft (HT-117) heparan sulphate (HS) proved to be the main cell surface glycosaminoglycan, in contrast to the chondroitin sulphate dominance in normal lymphoid cells. Using anti-proteoglycan (PG) antibodies and immunoelectronmicroscopy, two heparan sulphate proteoglycans (transferrin receptor (TfR) and fibroblast membrane type) and one chondroitin sulphate proteoglycan (articular cartilage type) molecule were co-localized as random clusters on the surface of these lymphoma cells. Double labelling revealed that during internalization, which occurred via endosomes avoiding the lysosomal system, the different proteoglycan (PG) antigens became separated. The TfR and fibroblast membrane type HSPG epitopes reappeared on plasmalemmal vesicles derived most probably from the multivesicular endosomes, representing a unique form of exocytosis. It is suggested that different cell membrane PGs are integrated into subunits of yet unknown function in these human non-Hodgkin (B) lymphoma cells.

Topics: Animals; Antigens, Neoplasm; Epitopes; Flow Cytometry; Glycosaminoglycans; Heparitin Sulfate; Humans; Lymphoma, Non-Hodgkin; Mice; Mice, Inbred CBA; Microscopy, Immunoelectron; Neoplasm Transplantation; Proteoglycans; Transplantation, Heterologous