concanavalin-a and Peritonitis

The liver remains a hematopoietic organ after birth and can produce all leukocyte lineages from resident hematopoietic stem cells. Hepatocytes produce acute phase proteins and complement in bacterial infections. Liver Kupffer cells are activated by various bacterial stimuli, including bacterial lipopolysaccharide (LPS) and bacterial superantigens, and produce interleukin (IL)-12. IL-12 and other monokines (IL- 18 etc.) produced by Kupffer cells activate liver natural killer (NK) cells and NK1.1 Ag+ T cells to produce interferon-gamma and thereby acquire cytotoxicity against tumors and microbe-infected cells. These liver leukocytes and the T helper 1 immune responses induced by them thus play a crucial role in the first line of defense against bacterial infections and hematogenous tumor metastases. However, if this defense system is inadequately activated, shock associated with multiple organ failure takes place. Activated liver NK1.1 Ag+ T cells and NK cells also cause hepatocyte injury. NK1.1 Ag+ T cells and another T-cell subset with an intermediate T-cell receptor, CD 122+CD8+ T cells, can develop independently of thymic epithelial cells. Liver NK cells and NK1.1 Ag+ T cells physiologically develop in situ from their precursors, presumably due to bacterial antigens brought from the intestine via the portal vein. NK cells activated by bacterial superantigens or LPS are also probably involved in the vascular endothelial injury in Kawasaki disease.

Topics: Animals; Antigens, Bacterial; Cell Lineage; Child, Preschool; Concanavalin A; Gram-Positive Bacteria; Humans; Intestinal Absorption; Killer Cells, Natural; Kupffer Cells; Lipopolysaccharides; Liver; Liver Circulation; Lymphocyte Activation; Lymphokines; Macrophage Activation; Mice; Mice, SCID; Mucocutaneous Lymph Node Syndrome; Multiple Organ Failure; Neoplasm Metastasis; Neoplastic Cells, Circulating; Peritonitis; Receptors, Antigen, T-Cell; Receptors, Antigen, T-Cell, gamma-delta; Shock, Septic; Shwartzman Phenomenon; Superantigens; T-Lymphocyte Subsets; T-Lymphocytes, Cytotoxic; Th1 Cells

Murine peritoneal macrophages isolated from the lavage fluid after administration of thioglycolate and concanavalin A are presented by two populations of cells of different diameters. Polarization of macrophages into a proinflammatory (M1) phenotype is accompanied by an increase in number of small cells. Macrophages obtained after administration of thioglycolate demonstrate higher tendency to anti-inflammatory (M2) phenotype, while macrophages isolated after administration of concanavalin A are committed in the proinflammatory direction. Lactate level is increased in M1 macrophages in comparison with M2 cells, which indicates predominance of glycolytic metabolism. Macrophages obtained after administration of concanavalin A have reduced mitochondrial potential, which reflects a tendency to apoptosis. Autophagy activation and inhibition neutralize the differences in pro- and anti-inflammatory properties of polarized macrophages obtained after thioglycolate administration, but have less pronounced effect on macrophages obtained after administration concanavalin A. Autophagy inhibitor increases mitochondrial potential in non-polarized macrophages obtained after administration of concanavalin A. These results demonstrate divergent properties of macrophages obtained after administration of glycolate and concanavalin A due to the difference in the mechanisms of experimental peritonitis.

Topics: Animals; Cell Polarity; Concanavalin A; Disease Models, Animal; Macrophage Activation; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Peritonitis; Thioglycolates

Arginine deficiency and chronic inflammation may cause immune dysfunction. The authors previously showed that a pharmacological dose of parenteral arginine facilitates ornithine rather than nitric oxide production in subacute peritonitis. Herein, they investigated the effects of different doses of parenteral arginine supplementation on immunocytic subpopulation distribution and function.. Male Wistar rats that underwent cecal punctures for induction of subacute peritonitis were infused with conventional parenteral nutrition solution (1.61% of total calories as arginine) or solutions supplemented with low-, medium-, or high-dose arginine (2.85%, 4.08%, and 6.54% of total calories, respectively) for 7 days. Distributions of T cells, B cells, and monocytes/macrophages and cytokine productions of peripheral blood lymphocytes (PBLs) and splenocytes were analyzed.. There were no significant differences in circulating white blood cell numbers and serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ concentrations among groups. Serum nitrate/nitrite (NOx) and interleukin (IL)-2 levels were significantly decreased by arginine in a dose-dependent manner. Animals supplemented with parenteral arginine had significantly decreased productions of concanavalin (Con) A- and lipopolysaccharide (LPS)-stimulated TNF-α in PBLs and splenocytes, spontaneous IL-6 and LPS-stimulated IFN-γ in PBLs, and LPS-stimulated IL-6 in splenocytes. In addition, low-dose arginine significantly increased production of spontaneous IFN-γ in PBLs and splenocytes. High-dose arginine significantly increased spontaneous TNF-α, and Con A stimulated IL-4 and IL-6 in PBLs.. Parenteral arginine administration at approximately 4% of total calories may alter PBLs and splenocytic immunity, and >6% of total calories might not be of benefit in rats with subacute peritonitis.

Topics: Animals; Arginine; Chronic Disease; Concanavalin A; Cytokines; Deficiency Diseases; Dietary Supplements; Dose-Response Relationship, Drug; Immunity; Inflammation; Inflammation Mediators; Leukocytes; Lipopolysaccharides; Macrophages; Male; Nitrates; Nitrites; Parenteral Nutrition; Peritonitis; Rats; Rats, Wistar; Spleen

To assess the suitability of concanavalin-A-induced hepatitis as a model for investigating the relationships between hepatic disease and alterations in somnolence.. We characterized the sleep patterns of various strains of inbred mice undergoing ConA-induced inflammation.. Southern Illinois University School of Medicine, Springfield, IL.. Intravenous or intraperitoneal administration of concanavalin-A.. Inbred mice.. Intravenous and intraperitoneal administration of concanavalin-A both elicited strain-dependent changes in slow-wave sleep. ConA treatment also reduced spontaneous locomotor activity. ConA-induced changes in slow-wave sleep varied with dose, route of administration, and circadian period of administration. As compared with the other strains, C57BL/6J mice had lower serum concentrations of interferon-gamma at 8 hours after ConA administration.. These data provide the first demonstration that sleep enhancement and reduced locomotor activity accompany hepatic inflammation in mice.

Topics: Animals; Body Temperature; Chemical and Drug Induced Liver Injury; Concanavalin A; Injections, Intravenous; Interferon-gamma; Interleukin-6; Locomotion; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Peritonitis; Sleep, REM; Tumor Necrosis Factor-alpha

Macrophage hyperactivity has been suggested to play an important role in septic complications and the development of multiple organ failure. Intraperitoneal administration of macrophage stimulants, e.g., zymosan, induce a systemic inflammatory response, with concomitant gut origin sepsis, and organ dysfunction. However, little is known about alterations in endothelial permeability during macrophage hyperactivation. In the present study, the effect of macrophage hyperactivation on endothelial permeability, assessed by 125I-labeled HSA and 51Cr-labeled EDTA, and the difference between cytolytic and noncytolytic inflammatory macrophages induced by i.p. injection of .25 or .50 mg/g of zymosan, concanavalin A (Con A) or thioglycollate medium (TM) diluted in 4 mL of paraffin, as well as the potential relationship with the doses used, were evaluated in the rat. Overactivation of cytolytic inflammatory macrophages induced a pronounced alteration in endothelial barrier permeability, characterized by a decrease in whole body plasma volume and an increase in whole body interstitial fluid volume, while overactivation of noncytolytic inflammatory macrophages only induced leakage of proteins and plasma to several of the organs studied. Macrophage activators, like zymosan, Con A and TM, exhibited varying effects on endothelial permeability related to the dose used. The results in the present study imply that overactivation of cytolytic inflammatory macrophages may play an important role in endothelial barrier injury and that zymosan possesses a more potent effect as compared to Con A when administered at the same dose.

Topics: Animals; Blood-Brain Barrier; Capillary Permeability; Concanavalin A; Cytokines; Endothelium, Vascular; Injections, Intraperitoneal; Macrophage Activation; Macrophages, Peritoneal; Male; Peritonitis; Rats; Rats, Sprague-Dawley; Thioglycolates; Viscera; Zymosan

Adjuvant arthritis (AA) can be induced in Lewis rats by a single injection of either heat-killed Mycobacterium tuberculosis or the lipoidal amine CP20961. Concanavalin A (Con A)-stimulated T cells isolated from AA rats are able to adoptively transfer the disease to naive syngeneic recipients. It is unclear, however, whether these transferred cells traffic directly to the joint and initiate arthritis, or whether secondary host cells are responsible for activation of the disease. In the current investigation, T cells labelled with the vital fluorescent dyes Hoechst H33342 and Zynaxis PKH26-G were used to adoptively transfer adjuvant disease to naive recipients. At various stages of disease development sections of ankle joints, together with a range of soft tissues, were examined by fluorescence microscopy to determine the distribution of labelled donor cells in the recipients. Intensely fluorescent lymphocytes were observed in the liver, spleen and lymph nodes within 24 hr of adoptive transfer. Foci of such cells were clearly visible in the primary lymphoid tissues as late as 14 days after transfer. However, close examination of both ankle joint sections and patellar fat pad cells throughout the time-course of the study failed to detect any labelled cells at the lesion site. To develop these observations further, we performed adoptive transfers to nude Lewis rats (rnu/rnu) and found that they were only moderately sensitive and developed, at best, a transient arthritis. This observed difference could not be explained by a generalized lack of an inflammatory response, since we were able to elicit a zymosan peritonitis in the nude rats. However, in nude Lewis rats a striking increase in adoptively transferred AA was obtained after reconstitution with 4 x 10(8) naive syngeneic spleen cells. These combined observations suggest that a host-derived immune cell population is crucial for arthritis induction in the adoptive transfer system.

Topics: Animals; Arthritis, Experimental; Cell Movement; Cells, Cultured; Concanavalin A; Female; Immunocompromised Host; Liver; Lymph Nodes; Lymphocyte Activation; Lymphocyte Transfusion; Microscopy, Fluorescence; Patella; Peritonitis; Rats; Rats, Inbred Lew; Spleen; T-Lymphocytes

A delayed-type inflammatory response was evoked in mice using concanavalin A (Con A) as a stimulus, and the effect of various anti-inflammatory agents on the inflammation was examined. The intraperitoneal injection of Con A in the mouse resulted in the marked accumulation of leukocytes, especially macrophages, in the peritoneal cavity between 16 and 48 hr after the injection. Prior to the accumulation of macrophages, the chemotactic activity for macrophages appeared in the peritoneal fluid, and was associated with protein(s) in the molecular weight range from 10,000 to 100,000 daltons. When the effect of various agents on Con A-induced peritonitis was examined, neither anticomplementary agents (FUT-175 and K-76 COONa), bromophenacyl bromide, nordihydroguaiaretic acid nor indomethacin affected the generation of chemotactic activity and the accumulation of macrophages, suggesting that C5a, prostaglandins and leukotriene B4 are hardly involved in the Con A-induced macrophage accumulation. On the other hand, dexamethasone suppressed both the generation of chemotactic activity and the accumulation of macrophages. Taking into consideration the observation that the synthesis of macrophage chemotactic factors by mitogen-stimulated lymphocytes is inhibited by glucocorticoids, these results suggest that the macrophage chemotactic lymphokines might be involved in the accumulation of macrophages in Con A-induced peritonitis.

Topics: Animals; Anti-Inflammatory Agents; Chemotactic Factors; Chemotaxis; Complement C5; Complement C5a; Concanavalin A; Dexamethasone; Kinetics; Macrophages; Male; Mice; Molecular Weight; Peritonitis