concanavalin-a and Neutropenia

A case of chronic lymphoproliferative disorder is presented, wherein a morphologically homogeneous population of lymphoid cells displayed properties similar to those described for large granular lymphocytes (LGL). Besides their LGL-like phenotype (VEP 13+, OKM 1+, OKT 10+ Fc-IgG-receptor+, OKT 3-), the proliferating cells were cytotoxic to NK targets as well as to antibody-coated target cells. Clinically, our patient presented low-grade lymphocytosis, splenomegaly, neutropenia, hyperimmunoglobulinemia and recurrent infections. Based upon this and 32 similar cases reported in the literature, we conclude that lympho-proliferative disorders involving GL encompass a variety of clinical entities, ranging from reactive GL lymphocytoses to overt lymphocytic malignancies.

Topics: Adult; Aged; Antibodies, Monoclonal; Bone Marrow; Concanavalin A; Female; Humans; Hypergammaglobulinemia; Isoantigens; Killer Cells, Natural; Leukemia; Lymphocyte Activation; Lymphocytes; Lymphocytosis; Male; Microscopy, Electron; Middle Aged; Neutropenia; Phenotype; Phytohemagglutinins; Receptors, Fc; Receptors, IgG

Lung cancer is one of the most important avoidable causes of death around the world, the most widespread carcinoma, with a very poor prognosis, and is the leading cause of cancer death in both developed and developing countries. We report morphological and biological behavior characteristics of a tumor that arose in only one BALB/c mouse of an experimental group treated with urethane, a chemical lung-tumorigenic agent. Morphological and immunochemical analysis indicated phenotypic compatibility with a lung adenocarcinoma. The tumor was named LAC1 (lung adenocarcinoma 1). Implant success in eight LAC1-bearing mice generations was 100%, with a fast evolution (58 survival days) and good metastatic capacity (41% of animals with metastases). The tumor induced a paraneoplastic syndrome characterized by anemia, neutrophilia, cachexia, splenomegaly and thymic atrophy. The lymphoproliferation to Con A was altered in tumor-bearing mice. This lung adenocarcinoma may be a useful experimental model for studying tumor progression, paraneoplastic syndromes and immunology in carcinogenic studies.

Topics: Adenocarcinoma; Animals; Cell Proliferation; Cells, Cultured; Concanavalin A; Erythrocyte Count; Hematocrit; Immunohistochemistry; Leukocytes, Mononuclear; Lung Neoplasms; Mice; Mice, Inbred BALB C; Models, Animal; Neoplasm Transplantation; Neutropenia; Organ Size; Splenomegaly; Thymus Gland; Urethane

Leukocyte infiltration into the liver is paramount to the development of liver injury in hepatitis. Hepatitis occurring after the administration of Con A in mice is felt to be a T lymphocyte-mediated disease. In this study, we report that neutrophils are the key initiators of lymphocyte recruitment and liver injury caused by Con A. The objectives of this study were to investigate the involvement of neutrophils in Con A-induced hepatitis in vivo via intravital microscopy. After Con A administration, we observed a significant increase in leukocyte rolling flux, a decrease in rolling velocity, and an increase in leukocyte adhesion to the hepatic microvasculature. Fluorescence microscopy identified that within 4 h of Con A administration only a minority of the recruited leukocytes were T lymphocytes. Furthermore, immunohistochemistry showed a significant increase in neutrophils recruited to the liver post-Con A treatment in association with liver cell damage, as reflected by elevated serum alanine aminotransferase levels. Using flow cytometry, we observed that Con A could bind directly to neutrophils, which resulted in a shedding of L-selectin, an increase in beta(2)-integrin expression, and the production of reactive oxidants. Following neutrophil depletion, a significant inhibition of Con A-induced CD4+ T lymphocyte recruitment to the liver resulted and complete reduction in hepatic injury, as assessed by serum alanine aminotransferase levels. In summary, the present data support the concept that neutrophils play an important and previously unrecognized role in governing Con A-induced CD4+ T cell recruitment to the liver and the subsequent development of hepatitis.

Topics: Animals; Antibodies, Monoclonal; CD4-Positive T-Lymphocytes; Cell Movement; Concanavalin A; Down-Regulation; Hepatitis, Animal; Injections, Intravenous; Liver; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Fluorescence; Microscopy, Video; Neutropenia; Neutrophil Activation; Neutrophil Infiltration; Neutrophils; Oxidants; Protein Binding; Reactive Oxygen Species

We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (P < 0.01 for all parameters) but had no discernible effect on platelet count. In DDS-treated mice, the proliferative response of splenic T cells to concanavalin A was > or = 35% higher than that manifested by splenocytes from vehicle-treated control mice. ZDV at 240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-dependent and statistically significant (P < 0.01). Concurrent administration of DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS and ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administration of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated elevation in lymphoproliferative response. These data suggest interaction between DDS and ZDV in mice and indicate a need for caution in using DDS as long-term therapy in AIDS patients receiving ZDV.

Topics: AIDS-Related Opportunistic Infections; Anemia; Animals; Anti-HIV Agents; Antiprotozoal Agents; Bone Marrow; Concanavalin A; Dapsone; Dose-Response Relationship, Drug; Drug Interactions; Female; Leukopenia; Lymph Nodes; Lymphocyte Activation; Methemoglobinemia; Mice; Mice, Inbred BALB C; Neutropenia; Pneumonia, Pneumocystis; Thrombocytosis; Thymus Gland; Zidovudine

The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% VO2max on circulating leukocyte and lymphocyte subpopulations, epinephrine and cortisol concentrations, and the Con A-induced lymphocyte proliferative response was investigated in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7 +/- 1.5 yrs). Blood samples were taken 15 min before (07.15h) and immediately after exercise (10.00h), with three more samples taken during 6h of recovery (11.30, 13.00, 16.00h). Ten sedentary controls (34.7 +/- 1.0 ml.kg-1.min-1, 45.3 +/- 2.3 yrs) sat in the laboratory during testing and had their blood sampled at the same time points. Serum cortisol was elevated relative to controls for more than 3 h post-exercise, and correlated significantly with the 3-h post-exercise, and correlated neutrophil/lymphocyte ratio (r = 0.68, p < 0.001). The concanavalin A- (Con A) induced lymphocyte proliferative response was decreased relative to controls for more than 3 h post-exercise, and except for the immediate post-exercise time point, tended to parallel the decrease in T cell (CD3+) concentrations.

Topics: Adult; Cell Division; Concanavalin A; Epinephrine; Exercise Test; Humans; Hydrocortisone; Leukocyte Count; Leukocytes; Leukocytosis; Lymphocyte Activation; Lymphocyte Subsets; Lymphocytes; Lymphopenia; Male; Middle Aged; Neutropenia; Neutrophils; Oxygen Consumption; Running; T-Lymphocytes

Swainsonine, an indolizidine alkaloid, was recently reported to exhibit both antineoplastic and immunomodulatory activities (Humphries, M.J.; Olden, K. Asparagine-linked oligosaccharides and tumor metastasis. Pharmacol. Ther. 44:85-105; 1989). In this study, we show that systemically administered swainsonine promoted the proliferation of murine bone marrow (BM) cells. Animals that received swainsonine intravenously exhibited a significant increase (approximately 5-10 fold) in BM cellularity, engraftment efficiency, and colony forming unit activity using in vitro or in vivo assays. BM cells derived from swainsonine-treated animals or treated with swainsonine in vitro also exhibited a 4-5 fold increase in [3H]-thymidine incorporation, suggesting that a larger fraction of the cells was in the S-phase of the cell cycle. This provides the first evidence that swainsonine, which stimulates the production of cytokines by cells of the immune system, promoted the proliferation of BM progenitor cells. These results suggest that swainsonine could prove valuable in patients undergoing intensive chemoradiotherapy or autologous BM transplantation by decreasing or possibly eliminating leukopenia or myelosuppression often associated with these procedures; it may also be a useful probe to investigate the mechanism of normal hematopoieses.

Topics: Alkaloids; Animals; Bone Marrow; Bone Marrow Transplantation; Cell Division; Colony-Forming Units Assay; Concanavalin A; Dose-Response Relationship, Drug; Glycoproteins; Mannosidases; Mice; Mice, Inbred C57BL; Neutropenia; Swainsonine; X-Rays

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

The characteristics of cyclophosphamide-induced suppression of established ccll mediated immunity were studied in guinea pigs previously senstized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose-dependent peripheral lymphoctopenia and disproportionatley greater neutrophenia which was particularly striking at high doses of 20 mg/kg per day(approximaetly 200 mg/kg-2 per day). Lymphoctes remianing in the circulation of cyclophosphamide treeated aniamls showed a doses-dependent reduction to both in vitro proliferactive and macrophage migration inhibitory factor responses to tuberculin compared to lymphocte responses of controls. Proliferative responses to phytohemaggultinin and concanavalin a were not significatly suppressed. Additional studies showed that cyclophosphamide suppressed the porliferactive and migration inhibitroy factor responses to tuberculin of lymph node and splenic as well as cirulating lymphocte populations. These studies showed that relatively short-term cyclophospamide administration produced immunosuppresion by quantitative as well as qualitative changes in lymphocyte populations. Significant suppresion of lymphocte function, howerver, was achived only with doses of cyclophoshamide which also produced a severe neutropenia.

Topics: Animals; Concanavalin A; Cyclophosphamide; Dose-Response Relationship, Drug; Guinea Pigs; Immunity, Cellular; Immunosuppression Therapy; Lectins; Leukocyte Count; Lymph Nodes; Lymphocytes; Lymphopenia; Macrophage Migration-Inhibitory Factors; Macrophages; Neutropenia; Spleen; Tuberculin