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V Cattell

Publications and source records attributed to V Cattell.

66 records · Page 4Linked to original sources
PubMed1980

Focal mesangial proliferative glomerulonephritis in the rat caused by Habu venom: the effect of antiplatelet agents.

The effects of the antiplatelet agents aspirin (ASA), dipyridamole (DP) and prostacyclin (PGI2) on glomerulonephritis following Habu snake venom have been investigated. ASA greatly increases glomerular damage and PGI2 inhibits glomerular damage. DP suppresses glomerular proliferation. The results extend previous studies on platelet activity in this model and provide evidence that (1) glomerular injury involves a platelet/endothelial reaction and (2) glomerular proliferation is affected by an antiplatelet drug.

Animals↗
PubMed1979

Focal mesangial proliferative glomerulonephritis in the rat caused by Habu snake venom: the role of platelets.

Platelet aggregates are a prominent early feature in the glomerular lesions of focal mesangial proliferative glomerulonephritis induced by Habu venom. After venom injection the peripheral blood platelet count falls rapidly, and in vitro the venom causes platelet aggregation and release of 5-HT. The role of platelets in this model has been studied in rats depleted of platelets by antiplatelet serum administration. No effect on the early (24 h) glomerular damage was found. Mesangial proliferation which appears 2--3 days after glomerular injury was significantly inhibited in platelet-depleted rats. These results show that platelet activity does not initiate the mesangial injury in this model, but suggest that platelets or their products act as a stimulus to mesangial proliferation.

Animals↗
PubMed1978

The origin of glomerular crescents in experimental nephrotoxic serum nephritis in the rabbit.

The origin of glomerular crescents and diffuse hypercellularity was investigated in rabbits receiving a single intravenous injection of nephrotoxic serum. Experiments to demonstrate local glomerular proliferation included mitotic counting at intervals after nephrotoxic serum and autoradiography of kidneys 1 hour after pulse-tritiated thymidine labeling. There was an increase in local endocapillary proliferation between days 4 and 6 when severe diffuse hypercellularity developed. From days 8 to 13 during crescent formation there was considerable local epithelial proliferation. To assess the role of infiltrating bone marrow cells a new technique of renal transplantation in rabbits was developed. Kidneys from unlabeled donors were transplanted on either day 4 or day 9 into recipients prelabeled with tritiated thymidine, and labeled cells were sought in glomeruli of transplants 1 to 4 days later. Large numbers of labeled cells appeared on days 5 to 6 in areas of endocapillary hypercellularity in glomeruli of animals given transplants on day 4 indicating a significant influx of bone marrow cells. In contrast, in kidneys transplanted on day 9, few labeled cells were present in crescents on days 10 to 11. Autoradiographic labeling of mononuclear phagocytes in carrageenan granulomas and interstitial renal infiltrates in recipients were used as positive controls of bone marrow cell labeling. We conclude that in the early phase of diffuse hypercellularity there is considerable blood monocyte infiltration, whereas crescents which develop later are principally the result of glomerular epithelial cell proliferation.

Animals↗
PubMed1977

The mesangial cell in glomerulonephritis. I. Mechanisms of hypercellularity in experimental immune complex glomerulonephritis.

One-shot active immune complex glomerulonephritis was induced in rabbits by intravenous bovine serum albumin (250 mg. per kg.) and the mechanism of glomerular hypercellularity investigated. Most of the extra cells were mononuclear with few polymorphonuclear leukocytes. Fibrin was present in severe lesions. Glomerular mitoses were seen in normal kidneys but were more common in hypercellular glomeruli. This is direct evidence of local proliferation. Also, biopsies taken 1 hour after giving tritiated thymidine contained locally labeled cells. The mitotic rate and degree of local labeling both varied in proportion to the degree of hypercellularity. By electron microscopy both mesangial and endothelial cells were identified in mitosis. The majority of the mononuclear cells in the hypercellular glomeruli could not be identified by position or ultrastructure. Infiltration by nonglomerular cells was confirmed by the presence of macrophages, lymphocytes, and plasma cells.

Animals↗
PubMed1977

Focal mesangial proliferative glomerulonephritis in the rat caused by habu snake venom. A morphologic study.

A new model of focal mesangial proliferative glomerulonephritis in the rat has been produced by intravenous habu snake venom. Glomerulonephritis developed in 70% of rats surviving the first 6 hours after venom administration. The earliest ultrastructural change (10 minutes after venom) was the presence of loose platelet aggregates and free granules in the capillary lumen and mesangium. This was followed by dissolution of the matrix and endothelial damage. Between 4 and 24 hours, a characteristic focal and segmental ballooned lesion of glomerular capillaries developed. In these lesions, from 3 days onwards a segmental mesangial proliferation occurred, which persisted until sacrifice at 21 days.

Animals↗
PubMed1975

Hyperacute rejection of guinea-pig to rat cardiac xenografts. I. Morphology.

The morphological changes occurring in xenograft hyperacute rejection, using guinea-pig to rat cardiac transplants, have been studied. Ultrastructural evidence of platelet aggregation in myocardial capillaries and veins first occurred two minutes after revascularisation. Small amounts of fibrin, associated with platelet degranulation occurred at three minutes. From four minutes, platelet aggregates increased in number and endothelial damage first appeared in those vessels containing platelet aggregates. Rejection was complete by 12 minutes and platelet aggregates then filled many capillaries, veins, arterioles and arteries. Polymorphonuclear leucocyte infiltration was not seen.

Animals↗
PubMedDate not supplied

Inducible nitric oxide synthase induction in Thy 1 glomerulonephritis is complement and reactive oxygen species dependent.

Thy 1 glomerulonephritis (GN) is a rat model of complement-dependent immune mesangial injury with induced glomerular nitric oxide (NO) synthesis. To examine mechanisms of inducible nitric oxide synthase (iNOS) induction, we studied the effects of treatment with the antioxidant N-acetyl-cysteine (NAC) and soluble complement receptor 1 (sCR1). Thy 1 GN was induced by intravenous anti-Thy 1 antibody. Glomeruli were isolated and kidney tissue taken from 30 min to 24 h after induction. Nitrite (NO-2) synthesis, luminol chemiluminescence for reactive oxygen species (ROS), and iNOS and cytokine mRNA were assayed in isolated glomeruli. Mesangial injury (mesangiolysis) and leucocyte infiltration were quantitated on tissue sections. NAC (i.p. 1,000 mg/kg, 1 h prior to anti-Thy 1) reduced glomerular NO-2 synthesis (3.5 +/- 0.66 vs. untreated 8.2 +/- 1.1, p = 0.02), and iNOS mRNA expression, and abolished enhanced chemiluminescence. In vitro incubation of nephritic glomeruli with 20 mM NAC also suppressed nitrite production (4.7 +/- 0.8 vs. untreated 12.2 +/- 0. 7 nmol NO-2/2,000 glomeruli/48 h, p = 0.003), and chemiluminescence. In NAC-treated animals, neutrophil infiltration (0.5 +/- 0 vs. untreated 9.6 +/- 1.6 glomerulus, p = 0.0005), and macrophage infiltration (1.7 +/- 0.4 vs. untreated 12.0 +/- 0.1, p = 0.006) were abolished, and mesangiolysis was significantly reduced (45.9 +/- 1.3 vs. untreated 34.4 +/- 2.1 cells/glomerulus, p = 0.009). NAC did not inhibit anti-Thy 1 antibody deposition. C1q was unaffected, but C3 was reduced. sCR1 treatment prevented iNOS mRNA induction, the enhanced chemiluminescence, and the neutrophil infiltration at 1 h. IL-1beta and TNFalpha mRNAs were not affected by either NAC or sCR1. These results show that NAC inhibits iNOS induction and NO synthesis in this model, and suppresses ROS synthesis and injury. They suggest that complement-dependent ROS generation is the critical initiating event that follows fixation of anti-Thy 1 antibody.

Acetylcysteine↗
PubMedDate not supplied

Arginase in glomerulonephritis.

Arginase metabolizes L-arginine to L-ornithine and urea. Two arginase isoforms, AI (liver arginase) and AII (ubiquitously expressed, functions unknown), have been identified. It is clear that arginases potentially have important roles in addition to urea generation for high concentrations are present at inflammatory sites. Regulation occurs through cytokines, substrate competition and products of nitric oxide (NO) metabolism. The functions of arginases at inflammatory sites are unknown, but may include regulation of apoptosis and NO production and generation of structural and cellular protein precursors. In glomerulonephritis there is increased arginase activity in nephritic glomeruli following a pattern similar to that in wound healing. The level can be further increased by NO inhibition suggesting substrate competition. The potential sources in the inflamed glomerulus include infiltrating leucocytes and mesangial cells, and the predominant isoform expressed is AI (AII predominates under physiological conditions). The recent identification of different isoforms of arginase has been an important step towards understanding the significance of arginase activity in glomerulonephritis.

Animals↗
PubMedDate not supplied

Glomerular NO synthase activity in mesangial cell immune injury.

Ex vivo synthesis of nitrite (NO2-) by nephritic glomeruli provides evidence of induction of nitric oxide (NO) in glomerulonephritis (GN). In macrophage-associated GN, the major source is infiltrating macrophages. As induction of NO synthesis has now been shown in cultured mesangial cells, we have examined whether in vivo mesangial proliferation is a source of NO2-. Mesangial proliferative GN was induced by intravenous anti-Thy1.1 (monoclonal antibody ER4). Isolated glomeruli were assayed for NO2- synthesis and macrophage infiltration on day 4 (mesangiolytic phase) and on day 7 (mesangial proliferation). On day 4, but not on day 7, basal NO2- was increased (8.3 +/- 1.8, controls 0.7 +/- 0.1 nmol/2,000 glomeruli/48 h; p = 0.05) and there was macrophage infiltration (60 +/- 15; controls 14 macrophages/glomerulus). At both times NO2- was elevated by exogenous IL1 or LPS, more significantly on day 4 than on day 7. Thus, mesangial proliferative lesions are not a source of basal NO2-, and macrophages are the most likely source. However, NO2- can be induced in mesangial proliferative glomeruli by exogenous stimuli, findings similar to those reported in cultured mesangial cells. Irradiation experiments in normal rats show that stimulated NO2- synthesis is inhibited by macrophage depletion. Therefore in neither normal nor proliferative glomeruli is there evidence for mesangial cell production of NO2-.

Amino Acid Oxidoreductases↗
PubMedDate not supplied

Rat mesangial cells have a selective role in macrophage recruitment and activation.

In proliferative glomerulonephritis glomeruli are the target of an inflammatory reaction involving macrophage recruitment and activation. We examined the role of mesangial cells in this process. Supernatants from basal, IL-1, IFN-tau or LPS-stimulated rat mesangial cells (MCS) were tested for chemotactic, colony-stimulating and activation effects on macrophages in vitro. IL-1-stimulated MCS produced a macrophage chemoattractant (p = 0.007 compared with basal MCS) and MCP-1 mRNA was detected in IL-1-stimulated mesangial cells. LPS or IL-1-stimulated MCS produced colony-stimulating activity (LPS p < 0.05, IL-1 p < 0.01, compared with basal MCS or control supernatant, CS). Macrophage activation, assessed by nitric oxide generation, was suppressed. This evidence from functional bioassays supports a selective role for mesangial cells in the control of macrophage-induced glomerular injury, whereby activated mesangial cells participate in the recruitment and proliferation of infiltrating macrophages, and suppresses at least one field of macrophage activation, namely nitric oxide generation.

Animals↗