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J V Weinstock

Publications and source records attributed to J V Weinstock.

At least 91 records · Page 5Linked to original sources
PubMed1985

Induction of granuloma modulation in murine schistosomiasis mansoni by enteric exposure to schistosome eggs.

Enteric administration of antigen can induce systemic tolerance. In murine schistosomiasis mansoni, blood flukes produce eggs which enter the intestine. An immunologic phenomenon associated with this disease is a spontaneous diminution in the intensity of the granulomatous response in the liver, lungs, and colonic mucosa with chronic infection, which is termed modulation. It was determined whether modulation of liver granulomas could be induced by enteric immunization with schistosome eggs. Mice infected for 4 wk were immunized by injection of 25,000 eggs into cecal pouches. This induced modulation of liver granulomas by the eighth week of infection. Neither cecal injection of normal saline nor i.p. or subcutaneous injection of eggs could induce the modulatory process. Modulation could be adoptively transferred from enterically immunized donors by injection of spleen cells into infected recipients or into uninfected recipients with synchronous liver granulomas induced by the hepatic embolization of schistosome eggs. Spleen cells treated with anti-Thy-1.2 or anti-Lyt-1.1 and complement could no longer adoptively transfer modulation. These data show that enteric immunization with schistosome eggs can induce modulation of the liver granuloma by a cellular mechanism similar to that described for the natural infection.

Animals↗
PubMed1985

Angiotensin II inhibition of mitogen- and antigen-induced human blood mononuclear cell thymidine uptake.

Angiotensin-converting enzyme and other components of the angiotensin system may participate in the regulation of inflammation. We therefore studied the effects of angiotensin II on human mononuclear cell reactivity. 48 hr phytohemagglutinin (5 micrograms/ml)-stimulated cultures of mononuclear cells from 6 subjects revealed thymidine uptake of 84,525 +/- 18,923 cpm (mean +/- se). When cultures contained angiotensin II (10(-7) M), reactivity was decreased to 75,279 +/- 17,727 cpm (p less than 0.05, paired t-test). Depletion of monocytes by nylon wool filtration or Percoll density-gradient centrifugation revealed persistence of the effect. Tetanus toxoid (0.5 LfU/ml)-induced thymidine uptake (86,910 +/- 31,591 cpm) was also reduced by the presence of 10(-6) M angiotensin II (68,094 +/- 25,509 cpm, p less than 0.01, paired t-test) when angiotensin II was added on the fourth day of 5 day cultures. No angiotensin II effects were observed on unstimulated thymidine incorporation. These findings indicate that angiotensin II can inhibit antigen- and mitogen-induced mononuclear cell reactivity and suggest that angiotensin II, the product of angiotensin converting enzyme may be an inhibitor of human lymphocyte function.

Angiotensin II↗
PubMed1984

Captopril enhances in vitro human lymphocyte thymidine incorporation.

Angiotensin-converting enzyme activity is present in human sarcoid as well as murine schistosome granulomas. Inhibition of angiotensin-converting enzyme by captopril results in decreased granuloma size in animals. Since captopril is used clinically to treat hypertension, its effect on human lymphocyte thymidine incorporation was determined. It was found that 5 X 10(-5) M and 10(-4) M captopril enhances lymphocyte thymidine uptake induced by 25 micrograms/ml phytohaemagglutinin-P. This suggests that captopril can alter immunological reactivity in man and that angiotensin-converting enzyme may have an immunological function.

Captopril↗
PubMed1984

Granuloma macrophages in murine schistosomiasis mansoni generate components of the angiotensin system.

The angiotensin cascade was recently detected in liver granulomas of murine Schistosomiasis mansoni, suggesting an immunoregulatory role for angiotensins in inflammation. In this study, isolated liver granulomas were fractionated into macrophage or lymphocyte-eosinophil-rich populations to determine the cellular origin of these hormones. Immunoreactive angiotensins I, II, and III (AI, AII, and AIII) were detected in granuloma macrophage homogenates by radioimmunoassay and chromatography. No angiotensins were associated with the lymphocyte-eosinophil fraction. Isolated granuloma macrophages, but not the lymphocyte-eosinophil fraction, retained appreciable angiotensins when cultured in vitro and spontaneously released these peptides into the culture medium. Similarly, culture of these cells in the presence of exogenous angiotensinogen or AI resulted in additional AI and/or AII/III appearing in the medium. These data support the contention that granuloma macrophages generate angiotensins from both endogenous and exogenous substrates.

Angiotensins↗
PubMed1984

Angiotensin II stimulation of granuloma macrophage phagocytosis and actin polymerization in murine schistosomiasis mansoni.

In murine schistosomiasis, components of the renin-angiotensin system are present in isolated liver granulomas. Furthermore, granuloma macrophages have receptors for angiotensin II (AII). These observations with other evidence suggest that angiotensins function in immunoregulation. Since AII can stimulate actin-myosin interactions and since macrophages have contractile proteins, it was determined whether AII could alter the phagocytic activity of granuloma macrophages. AII, at concentrations which saturate AII receptors, enhanced phagocytic activity for both unopsonized and opsonized sheep red blood cells (RBC). Using a DNase inhibitory assay, it was also shown that similar concentrations of AII stimulated intracellular actin polymerization. Cytochalasin B, which impedes actin filament interactions, inhibited AII-stimulated phagocytosis. AII analogs, with little-known agonist activity, blocked AII-stimulated actin polymerization and phagocytosis of RBC and RBC opsonized with IgG. These data support the contention that AII binds to AII receptors on the macrophage and stimulates phagocytosis possibly through polymerization of intracellular actin.

Actins↗
PubMed1984

Functional angiotensin II receptors on macrophages from isolated liver granulomas of murine Schistosoma mansoni.

Isolated liver granulomas from mice infected with Schistosoma mansoni contain components of the renin-angiotensin system. Angiotensin II is a major biologically active component of this system. It was therefore determined whether inflammatory cells within the granuloma possessed receptors for this hormone. Specific binding of angiotensin II to isolated granuloma macrophages was demonstrated by both fluorescence and radioligand assays. The binding of 125I-angiotensin II was saturable, dependent on radioligand concentration, and reversible. Scatchard analysis of binding data suggested a Kd of 0.25 nM with 526 binding sites per cell. The natural analogs of angiotensin II, angiotensin I and III, only weakly competed for angiotensin II binding sites. Exposure of macrophages to appropriate binding concentrations of angiotensin II resulted in a rapid dose-dependent increase in intracellular cAMP. It is therefore concluded that granuloma macrophages possess functional receptors for angiotensin II.

Angiotensin II↗
PubMed1983

Isolated liver granulomas of murine Schistosoma mansoni contain components of the angiotensin system.

Angiotensin I (AI) and angiotensin II/III (AII/III) were detected by radioimmunoassay in homogenates of isolated liver granulomas from mice infected for 8 wk with Schistosoma mansoni. Angiotensin I converting enzyme (ACE) activity, which could be completely inhibited by captopril, a specific ACE inhibitor, was also present as determined by radioassay. Spontaneous angiotensin I-generating activity was detected in homogenates that received supplemental angiotensinogen (protein renin substrate). This activity was partly inhibited by pepstatin, an acid protease inhibitor, indicating the presence of angiotensinogenase(s). Trypsinization of homogenates resulted in some AI generation, which suggests that homogenates had AI precursor. Treatment of infected mice with MK421, another specific ACE inhibitor, decreased granuloma ACE activity and AII content and size. AII, and to a lesser extent AIII, inhibited mouse peritoneal macrophage migration in an in vitro assay. These data support the contention that components of the angiotensin system are in the granuloma and may serve a function in regulation of the inflammation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Organ-dependent differences in composition and function observed in hepatic and intestinal granulomas isolated from mice with Schistosomiasis mansoni.

In murine schistosomiasis mansoni, eggs deposited in the liver and intestines induce a cell-mediated granulomatous reaction. Previous studies have shown that maximal granuloma size differs in the liver and various segments of the gastrointestinal tract. The objective of this investigation was to isolate intestinal granulomas and to determine whether organ-dependent differences in cell composition and granuloma function exist. Intestinal granulomas representative of those in tissue were isolated by a combination of chemical and mechanical techniques. When dissociated by collagenase, these lesions yielded a viable heterogeneous population of inflammatory cells. Granulomas from the liver, colon, and ileum showed differences in cellular composition. Liver lesions contained the largest number of T and B lymphocytes, eosinophils, and mast cells whereas ileal granulomas comprised mostly macrophages. Immunofluorescence studies on frozen tissue sections revealed that T and B lymphocytes also displayed different patterns of distribution within granulomas from different tissues. In contrast to isolated cultured liver granulomas that produced MIF-like substances, isolated colonic and ileal granulomas had weak or no MIF activity. It thus appears that granuloma formation in various organs is influenced by local factors that could affect the ultimate resolution of the lesions.

Animals↗
PubMed1983

Modulation of granulomatous hypersensitivity. V. Participation of histamine receptor positive and negative lymphocytes in the granulomatous response of Schistosoma mansoni-infected mice.

The possible role of histamine and histamine-receptored inflammatory cells in the granulomatous response of Schistosoma mansoni-infected mice was examined. Special staining revealed the presence of numerous mast cells, many partially degranulated within the liver granulomas. Treatment of infected mice with cimetidine (an H2 receptor antagonist) enhanced, and diphenyhydramine (an H1 receptor antagonist) decreased the granulomatous response. Fluorescein-labeled histamine-rabbit serum albumin conjugate (H-FRSA) and unlabeled conjugate (H-RSA)-coated culture plates were used to identify and isolate cells with histamine receptors. A large proportion of granuloma macrophages, lymphocytes, eosinophils, neutrophils, and splenic lymphocytes had histamine receptors. Elution of adherent cells from H-RSA-coated culture plates with H1 or H2 receptor antagonists suggested that receptors on granuloma cells were predominately H1 with some granuloma lymphocytes bearing H2-type receptors. Splenic lymphocytes from infected mice were functionally divided according to the presence or absence of histamine receptors on their cell surface. Receptor-negative lymphocytes appeared to mediate SEA-stimulated MIF production (TDH cells) and participated in the adoptive transfer of suppression of granulomas (TH cells). Whereas, TS cells appeared to have histamine receptors. Based on these data, it is inferred that lymphocytes that regulate lymphokine production (TS cells) within the granuloma may be triggered via their histamine receptors to exert suppressive activity.

Animals↗
PubMed1983

Modulation of granulomatous hypersensitivity. VI. T lymphocyte subsets influence mast cell density in liver granulomas of Schistosoma mansoni-infected mice.

In murine schistosomiasis mansoni, a complex series of cell-cell interactions involving T cell subclasses regulates the intensity of the inflammatory granulomatous response. Recent evidence suggests that granuloma mast cells also participate in the regulatory process by the release of histamine. The current study was performed to determine factors that affect the number of granuloma mast cells. More mast cells were detected in liver granulomas from chronically (20-wk) as opposed to acutely (8-wk) infected mice. Adoptive transfer of spleen cells from 20-wk-infected donors into acutely (6-wk) infected recipients increased granuloma mast cell density. Treatment of spleen cells with anti-Thy-1.2 or anti-Lyt-1.1 antiserum and complement, but not anti-Lyt-2.1 or normal mouse serum, abrogated adoptive transfer-induced, augmentation of granuloma mast cell density. Treatment of acutely infected animals with cyclophosphamide or cimetidine (H2 antagonist enhanced granuloma mast cell density. These data suggest that granuloma mast cell density is dependent upon subsets of T lymphocytes.

Animals↗
PubMed1982

Alteration of granuloma angiotensin I-converting enzyme activity by regulatory T lymphocytes in murine schistosomiasis.

Granulomatous inflammatory lesions in murine schistosomiasis mansoni undergo a spontaneous diminution at the chronic phase of the disease concurrent with an increase in angiotensin I-converting enzyme (ACE) activity. The objective of this investigation was to determine whether T cells influence ACE activity within the granulomas. Cyclophosphamide and cimetidine treatments of mice, which augment delayed-type hypersensitivity reactions, enhanced liver granuloma size and decreased granuloma ACE activity. The suppression of liver granuloma by the adoptive transfer of spleen cells from chronically infected, immunomodulated mice into recipients with acute infection increased ACE activity of granulomas and granuloma macrophages. The increased ACE activity was dependent upon the transfer of Thy 1.2+ splenic lymphocytes. The level of the ACE activity was proportionate to the number of administered spleen cells. Thus, the level of ACE activity within the egg-induced granuloma is dependent upon T lymphocytes present in the spleen and granulomas of infected animals.

Animals↗
PubMed1982

Production of angiotensin I converting enzyme by liver granuloma macrophages of Schistosoma mansoni infected mice.

Angiotensin I converting enzyme activity is detectable in serum and isolated liver granulomas of mice infected with Schistosoma mansoni. At the chronic phase of the infection (20 wk) the intensity of the granulomatous response spontaneously diminishes. Concomitantly, an increase in angiotensin I converting enzyme activity is observed. The objective of this investigation was to determine the source of this elevated angiotensin I converting enzyme activity. In chronically infected mice, measurements showed that angiotensin I converting enzyme activity in hepatic venous blood was higher than that of peripheral venous blood. In contrast, normal mice demonstrated no difference in regional venous angiotensin I converting enzyme activity. Isolated liver granulomas cultured in vitro released angiotensin I converting enzyme into the culture medium. When granulomas were dispersed into single cell suspension, angiotensin I converting enzyme activity was traced to the adherent cell fraction. Both granulomas and adherent cells from granulomas of the chronically (20 wk) infected mice secreted far more angiotensin I converting enzyme than those from animals with acute (8 wk) infection. Cycloheximide partially inhibited enzyme release. We conclude that in murine schistosomiasis, angiotensin I converting enzyme is produced by the granuloma macrophage. The enzyme is released from the granuloma into the circulation probably resulting in increased serum angiotensin I converting enzyme activity. The role of elevated angiotensin I converting enzyme activity within the lesion as well as the circulation remains to be elucidated.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1982

Lymphocyte reactivity to Crohn's ileal homogenates.

This study was undertaken to demonstrate whether lymphocytes derived from patients with Crohn's disease and their household contacts would demonstrate increased reactivity upon exposure to tissue homogenates prepared from the terminal ileum of patients with Crohn's disease. It was demonstrated that 4 of 18 patients, 9 of 30 household contacts, and 0 of 13 control subjects exhibited statistically greater lymphocyte thymidine incorporation in response to Crohn's tissue homogenates (contacts vs control, P = 0.025) [Fisher Exact Test (FET)]. However, homogenates prepared from the terminal ileum of control subjects without inflammatory bowel disease also induced lymphocyte reactivity in 1 patient, 5 contacts, and 1 control subject. Factors may be present in homogenates prepared from human terminal ileum which induce lymphocyte reactivity in some patients with Crohn's disease and household contacts.

Adult↗
PubMed1981

Angiotensin-converting enzyme in Crohn's disease and ulcerative colitis.

The relationship between serum angiotensin-converting enzyme activity and inflammatory bowel disease was investigated in 37 patients who had Crohn's disease, 31 patients who had ulcerative colitis, and 104 control subjects. The enzyme activity tended to be depressed in Crohn's ileitis (P less than 0.05) and colitis, but not in Crohn's ileocolitis and ulcerative colitis. No increase in enzyme activity was observed in Crohn's disease ileum or colon or in ulcerative colitis colon. The granulomatous inflammation in Crohn's disease differs from that in sarcoidosis, in which striking elevation of angiotensin-converting enzyme is present in granulomatous tissue and frequently in serum.

Adult↗
PubMed1981

Effect of SQ 14225, an inhibitor of angiotensin I-converting enzyme, on the granulomatous response to Schistosoma mansoni eggs in mice.

Murine schistosomiasis is a granulomatous disease associated with high serum and granuloma angiotensin I-converting enzyme (ACE) activity. SQ 14225, a specific competitive inhibitor of ACE, was administered to normal mice and mice infected with Schistosoma mansoni to determine whether this compound could inhibit granuloma ACE activity and modify the size of the granulomatous response to schistosome eggs. Peroral administration of SQ 14225 for 5 wk to infected mice with peak granulomatous responses decreased ACE activity in isolated liver granulomas. Treated mice demonstrated a decrease in granuloma size in the liver, colon, and ileum, and hydroxyproline concentration of isolated liver granulomas was increased. Mean diameters of synchronous pulmonary granulomas, induced by the pulmonary embolization of schistosome eggs into normal and sensitized mice, were decreased by a similar dose of SQ 14225. Withdrawal of SQ 14225 from unsensitized mice with 2-wk-old synchronous pulmonary granulomas induced an increase in inflammation. Infected, but not normal mice receiving SQ 14225 demonstrated reduced portal pressure, liver weight, and body weight. Both normal and infected mice experienced dipsogenesis, expanded intravascular volume, and increased serum ACE. These observations suggest that SQ 14225 can partially inhibit the granulomatous response to schistosome eggs and the pathological manifestations of schistosomiasis. It is possible that ACE has an inflammatory role in granulomatous inflammation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1981

Alteration of the granulomatous response in murine schistosomiasis by the chronic administration of captopril, an inhibitor of angiotensin-converting enzyme.

Captopril (SQ 14225) is an inhibitor of angiotensin I-converting enzyme (ACE). Mice with schistosomiasis form granulomas in the liver and intestines that have high ACE activity. We determined whether chronic oral captopril administration would alter the granulomatous response. Infected mice treated with captopril had a dose-dependent decrease in liver granuloma size. Chronic peroral administration of drug induced a sustained decrease in granuloma ACE activity and size which was reversible upon drug withdrawal. The drug was most effective during the acute phase of infection. Granuloma size in the colon, ileum, and ileal Peyer's patches was also decreased by treatment. Ileal granulomas were affected the least. Liver, colon, ileum, and ileal Peyer's patches demonstrated natural differences in size of response to schistosome eggs. Synchronous hypersensitivity granulomas, containing no ACE activity, were generated by the pulmonary embolization of methylated bovine serum albumin-coated, Sepharose beads into sensitized mice. Captopril treatment did not affect the size of these lesions. Sustained improvements in portal pressure, body and liver weight, and water consumption were seen in treated mice. We conclude that captopril induces sustained suppression of the granulomatous response in schistosome-infected mice, which results in decreased morbidity. Circumstantial evidence suggests that captopril influences inflammation through the competitive inhibition of ACE.

Angiotensin-Converting Enzyme Inhibitors↗