concanavalin-a and Nephritis

Changes in the glycoconjugates of renal tubules associated with tubular damage were studied by lectin histochemistry, and their possible significance was determined. The excretion of various saccharides in tubular casts may also serve as markers of renal tubular damage. Renal tissues from 55 cases with various glomerular diseases including ten controls were studied. The patients were divided into two groups: one with tubulointerstitial lesions (TILs) (30 cases), and the other without (15 cases). Our results showed a wide spectrum of changes, predominantly in the disease group with TILs. The brush border of the proximal tubules showed significantly increased staining with Triticum vulgaris (WGA) and decreased staining with Canavalia ensiformis (Con A) lectins in both disease groups. The distal tubules revealed a significant increase in the apical and a decrease in the basal staining with Arachis hypogaea (PNA) and WGA lectins, respectively, in cases with TILs. The significant decrease in the basal domain staining was also seen with WGA lectin in cortical ducts. The vulnerability of various segments of the tubules in the process of TILs was clearly demonstrable. It appeared that the distal tubules were the most vulnerable anatomical segments around which the TILs began and later spread to involve other segments of tubules.

Topics: Concanavalin A; Glycoconjugates; Histocytochemistry; Humans; Kidney Tubules; Lectins; Lupus Nephritis; Nephritis; Nephritis, Interstitial; Peanut Agglutinin; Phytohemagglutinins; Plant Lectins; Staining and Labeling; Wheat Germ Agglutinins

These experiments evaluated extraglomerular sites of renal immune complex (IC) deposition and specific features of host capability to remove these IC. Ex vivo perfusion of rat kidneys with the endothelium binding lectin concanavalin A (con A) followed by rabbit anti con A IgG results in a subendothelial IC nephritis in glomerular capillaries (GC) and diffuse IC formation with complement (C3) deposition in peritubular capillaries (PC). Histologic, immunofluorescence, and ultrastructural studies were performed at 10 minutes and 1, 4, and 24 hours after perfusion. At 10 minutes, strong linear binding of con A, rabbit IgG, and rat C3 to the endothelium was detected by immunofluorescence in both GC and PC. In GC this was followed by endothelial cell swelling and denudation (1 hour) with platelet and neutrophil infiltration and formation of subendothelial IC deposits which persisted at 4 and 24 hours. In contrast, some PC endothelial swelling was also present at 10 minutes and 1 hour, but ICs (IgG, con A, C3) were capped and shed into capillary lumina at 1 to 2 hours with complete clearance of IC by 4 hours. Selective neutrophil depletion, by antisera and irradiation, and complement depletion with cobra venom factor, delayed clearance of PC IC by several hours but complete clearance of IC with restored structural integrity of PC was still achieved by 24 hours. Platelet depletion had no effect on PC IC clearance. These studies demonstrate a model for study of PC IC. Such a model may aid our understanding of lupus nephritis in which extensive GC IC deposits associated with severe inflammatory injury may coexist with PC deposits. Efficient clearance of IC in PC compared with GC may be due to differences in hemodynamic forces, amounts of IC formed in each of these sites, differences in binding of IC to subendothelial basement membrane, or phenotypic specialization of the endothelium lining these two different capillary beds.

Topics: Animals; Antibodies; Antigen-Antibody Complex; Blood Platelets; Capillaries; Concanavalin A; Endothelium, Vascular; Ferritins; Fluorescent Antibody Technique; Immunoglobulin G; Kidney Tubules; Leukocytes; Male; Nephritis; Rats; Rats, Inbred Strains

Although circulating phagocytic cells are important mediators of glomerular injury, their recruitment mechanisms are not completely understood. In this study, the intraglomerular trafficking of leukocytes was characterized in a rat model of acute glomerular injury induced by nephrotoxic serum (NTS). Polymorphonuclear (PMN) cells infiltrated, then disappeared rapidly, reaching a peak at 2 hr. By 6 hr the PMN migration had almost reversed but small numbers persisted until Day 7. The monocyte influx began almost simultaneously but was of lesser magnitude. However, the number of ED-1+ monocytes increased progressively from 60 min to reach a plateau by Day 2 and persisted to the end of the study (Day 28). Quantitation of intraglomerular Ia+ cells suggested in situ activation of monocytes within the glomeruli. Increased Ia+ cells were first evident on Day 2. By Day 5, 80% of the intraglomerular macrophages were Ia+. Complement depletion with cobra venom factor abrogated early albuminuria, delayed the initial PMN influx, but failed to attenuate monocyte migration. T lymphocytes appeared briefly between 10 min and 2 hr. In vitro proliferation study failed to demonstrate lymphocyte sensitization to glomerular basement membrane (GBM) antigens. A unique population of cells (OX19 OX8+), possibly representing natural killer cells, was present from Day 1 to Day 14. During the secondary wave of proteinuria (autologous phase), all leukocytes had disappeared except for macrophages and a small number of OX19-, OX8+ cells. A complex intraglomerular migration of leukocytes was triggered by the binding of nephrotoxic antibodies to GBM antigens. We speculate that this cascade involves several cell-to-cell interactions necessary for the full expression of glomerular injury.

Topics: Animals; Basement Membrane; Cell Division; Cell Movement; Complement System Proteins; Concanavalin A; Disease Models, Animal; Fluorescent Antibody Technique; Kidney Cortex; Kidney Glomerulus; Leukocytes; Male; Monocytes; Nephritis; Neutrophils; Phagocytes; Proteinuria; Rats; Rats, Inbred Lew

To determine whether patients with systemic lupus erythematosus (SLE) and active nephritis have more profound defects in suppressor cell activity, we studied concanavalin A (Con A)-induced suppressor cell activity (SCA) in 12 patients with lupus nephritis (LN) and 11 patients with chronic mesangial proliferative glomerulonephritis (CGN) without renal insufficiency. The levels of Con A-induced SCA were decreased in patients with LN compared with those in normal controls and those in CGN patients and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, the mean responses of Con-A-induced SCA in CGN patients with or without NS did not differ from normal subjects. These findings may lend further insight into the understanding of the immunoregulatory defect in LN.

Topics: Adolescent; Adult; Cell Communication; Concanavalin A; Female; Humans; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Nephritis; T-Lymphocytes, Regulatory

The present study failed to show a significant association of Henoch-Schönlein Purpura Nephritis (HSPN) with any of the HLA specificities tested. No abnormalities pertaining to in vitro lymphocyte blastogenesis to various nonspecific mitogens (PHA, PWM, ConA) were detected during the clinical remission of HSPN. During the active phase, HSPN patients developed significant lymphocytosis. The absolute numbers of OKT4+ cells (helper cells) were significantly increased but absolute numbers of OKT8+ cells (suppressor cells) were not altered.

Topics: Adolescent; B-Lymphocytes; Child; Child, Preschool; Concanavalin A; HLA Antigens; HLA-B35 Antigen; Humans; IgA Vasculitis; Lymphocyte Activation; Mitogens; Nephritis; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Using the method of concanavalin A (Con a) inducible suppressor activity the peripheral mononuclear cells (PMC) of 17 patients with Mesangial IgA nephritis, 13 patients with idiopathic mesangial proliferative glomerulonephritis but with no IgA deposits on immunofluorescence (Non-IgA nephritis) and 18 healthy subjects were studied. DNA synthesis was measured by incorporation of 3H Thymidine. The mean suppression index (S.I.) of 0.94 +/- 0.08 (SEM) in the IgA nephritic patients was significantly different from that of the non-IgA nephritic patients (0.67 +/- 0.05) (P less than 0.01) as well as the group of normal healthy controls (0.64 +/- 0.05) (P less than 0.0025). The data show that patients with IgA nephritis have abnormal suppressor cell function and suggest an autoimmune basis in the pathogenesis of IgA nephritis.

Topics: Adult; Concanavalin A; Female; Humans; Immunoglobulin A; Kidney Glomerulus; Male; Nephritis; T-Lymphocytes, Regulatory

The response of peripheral blood lymphocytes to the phytomitogens, PHA, Con A, and PWM, was evaluated in 30 SLE patients and in 30 age, sex, and race-matched controls using dose and time responses. The proliferative response to the three phytomitogens was not depressed in this group of subacute and chronic SLE patients. Active lupus nephritis and a slow acetylator phenotype were associated with a decreased lymphocyte response. The incidence of a slow acetylator phenotype in spontaneous SLE was 68%. In interpreting the lymphocyte response to phytomitogens, the importance of a clear definition of the SLE group under study, the activity of the disease, and treatment status are emphasized.

Topics: Adolescent; Adult; Aged; Concanavalin A; Female; Humans; Immunity, Cellular; Lectins; Lupus Erythematosus, Systemic; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Nephritis; Sulfamethazine