concanavalin-a and Agranulocytosis

Schwachman's syndrome is characterised by pancreatic insufficiency and frequent infections. Absolute polymorphonuclear leucocyte (PMN) counts are low in many patients, and the PMN show abnormal chemotaxis. It was postulated that a cytoskeletal defect might underlie these abnormalities, and a cytoskeleton-dependent function, the surface distribution and mobility of concanavalin-A receptors, was studied on neutrophils from Schwachman's syndrome patients. Approximately a third of the neutrophils in each patient showed a patched distribution of fluorescein-conjugated concanavalin A (FITC-con A) rather than the usual diffuse staining pattern. These patched neutrophils also bound larger amounts of FITC-con A than diffusely stained or capped PMN from the same patient. Antitubulin treatment did not alter the proportion of patched PMN. These findings suggest that a cytoskeletal defect underlies the patching of FITC-con A on the PMN surface. This defect could also contribute to the abnormal chemotaxis and frequent infections found in Shwachman's syndrome patients.

Topics: Adolescent; Agranulocytosis; Cell Membrane; Chemotaxis; Child, Preschool; Concanavalin A; Cytoskeleton; Disease Susceptibility; Exocrine Pancreatic Insufficiency; Humans; Infections; Neutropenia; Neutrophils; Receptors, Concanavalin A; Staining and Labeling; Syndrome

Five of 39 (13%) women treated with adjuvant combination chemotherapy plus levamisole immunotherapy after mastectomy for Stage II or III breast cancer developed levamisole-induced granulocytopenia. This complication occurred in each of the women between six and ten weeks after the completion of six months of combination chemoimmunotherapy when they were taking levamisole alone. Although none of the patients had an HLA B-27 locus and leukoagglutinins could not be demonstrated, complement-dependent, IgM mediated, peripheral destruction of granulocytes was documented using a microgranulocytotoxicity assay. In addition, a factor(s) present in serum from patients developing levamisole-induced granulocytopenia caused suppression of bone marrow granulocyte progenitor cells (CFU-C). The possible relationships between levamisole-induced peripheral granulocyte destruction and bone marrow CFU-C suppression are discussed.

Topics: Acute Disease; Adult; Aged; Agranulocytosis; B-Lymphocytes; Breast Neoplasms; Colony-Forming Units Assay; Concanavalin A; Cyclophosphamide; Cytotoxicity, Immunologic; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Hemagglutination Tests; Humans; Levamisole; Methotrexate; Middle Aged; Phytohemagglutinins; T-Lymphocytes