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J V Weinstock

Publications and source records attributed to J V Weinstock.

At least 73 records · Page 4Linked to original sources
PubMed1990

Release of substance P by granuloma eosinophils in response to secretagogues in murine schistosomiasis mansoni.

In murine schistosomiasis, granulomas form around parasite ova which lodge in the liver and intestines. The granulomas contain eosinophils which produce substance P. In order to demonstrate substance P release by individual granuloma eosinophils and mechanisms regulating this release, a reverse hemolytic plaque assay was developed. Release of substance P was demonstrated by plaque formation around granuloma eosinophils only when a specific substance P antiserum was used. Few cells released substance P in the basal state. However, eosinophils produced plaques in the presence of calcium ionophore A23187 or histamine. Plaque size and number were dependent upon secretagogue concentration. It is thus concluded that granuloma eosinophils can release substance P in response to both pharmacological and physiological agents.

Animals↗
PubMed1990

Macrophages within the granulomas of murine Schistosoma mansoni are a source of a somatostatin 1-14-like molecule.

Inflammatory cells secrete some neuropeptides that function as immunomodulators. Somatostatin has immunoregulatory properties. It is unknown whether immune cells make somatostatin. Intricate intercellular communications govern the granulomas of murine Schistosoma mansoni. These granulomas synthesize several neuropeptides. Thus, it was determined whether somatostatin is in these inflammatory lesions. Granulomas, which were isolated from the livers of infected mice, contained somatostatin 1-14 as shown by radioimmunoassay and chromatography. Immunostaining localized immunoreactive somatostatin and pre-prosomatostatin to granuloma macrophages. Granuloma macrophages cultured in vitro released immunoreactive somatostatin. Calcium ionophore A23187, which promotes macrophage secretion, increased somatostatin in the culture supernatants. Thus, the granulomas have a molecule with somatostatin 1-14-like properties that is possibly a secretory product of the granuloma macrophage.

Animals↗
PubMed1990

Increased colonic mucosal angiotensin I and II concentrations in Crohn's colitis.

To define a potential role for the angiotensin system in Crohn's colitis, the colonic mucosal levels of angiotensin I and II were measured in endoscopic biopsy samples from patients with active Crohn's colitis (n = 20), ulcerative colitis (n = 13), other forms of colitis (n = 3), and normal controls (n = 17). Colonic mucosal levels of angiotensin I and II were greater in patients with Crohn's colitis than in normal subjects (p less than 0.001 and p less than 0.001, respectively). Mucosal levels of angiotensin I and II were also higher in Crohn's colitis than in ulcerative colitis (p less than 0.001 and p less than 0.001, respectively), and levels of angiotensin II were higher in Crohn's than in other forms of colitis (p = 0.014). Mucosal levels of angiotensin I and II correlated well with the degree of macroscopic inflammation in Crohn's colitis (r = 0.86, p less than 0.001 and r = 0.68, p less than 0.001, respectively). Mucosal levels of angiotensin I correlated fairly well with the Crohn's Disease Activity Index (r = 0.46, p less than 0.05) while angiotensin II levels correlated poorly. These studies suggest that angiotensin I and II may have a role in the inflammation associated with Crohn's colitis.

Angiotensin I↗
PubMed1989

Tachykinin production in granulomas of murine schistosomiasis mansoni.

Preprotachykinins, the products of one gene, are the precursor molecules of three mammalian tachykinins called substance P (SP), substance K (SK), and neuropeptide K. An additional mammalian tachykinin, neurokinin B, has also been described. SP and possibly other tachykinins may modulate immunologic responses. Granulomas that form around parasite ova in murine schistosomiasis were examined for tachykinins. Tachykinins were extracted from granulomas by boiling or with detergent. Extracts examined by RIA and HPLC contained only immunoreactive SP. Granulomas were dispersed with collagenase and cultured in vitro for up to 4 h. Only immunoreactive SP appeared in the culture medium. SP immunoreactivity localized solely to granuloma eosinophils as demonstrated by a sensitive immunohistochemical technique. An antiserum that recognized SK, neuropeptide K, and neurokinin B, but which possessed low reactivity to SP, also stained these cells. Only prior absorption of each antiserum with the appropriate synthetic neuropeptide would abrogate the immunostaining. This suggested that tachykinins other than SP were present within these cells. However, results of in situ hybridization experiments intimated that eosinophils produced predominantly preprotachykinin mRNAs which encode SP but are devoid of the SK/neuropeptide K sequence. It is concluded that granuloma eosinophils make predominantly SP in deference to other tachykinins, and that tachykinins other than SP are unlikely to be important in the regulation of the early granulomatous response of murine schistosomiasis.

Animals↗
PubMed1989

Alteration of the angiotensin cascade by schistosome ova.

In schistosomiasis mansoni, the parasite ova lodge in the microvasculature of organs and induce granulomas. It is assumed that factors derived from the ova activate circulating mediators that help initiate the inflammation. Components of the angiotensin system are in plasma and may have a role in inflammation. Therefore, whether ova could alter plasma angiotensin metabolism was determined. Incubation of 1 ml of plasma with up to 1,000 ova increased plasma AII (angiotensin II) concentration as measured by radioimmunoassay. HPLC analysis of [125I]AI (angiotensin I) metabolism in plasma suggested that ova can increase the conversion of AI to AII. Ova did not alter plasma angiotensin-converting enzyme activity. The ova themselves did not contain or release components of the angiotensin system during culture. It is concluded that interaction of ova with plasma can affect the angiotensin cascade.

Angiotensin II↗
PubMed1988

Eosinophils from granulomas in murine schistosomiasis mansoni produce substance P.

Granulomas are chronic, usually focal, tissue-destructive inflammatory reactions that usually form around slowly degradable, poorly soluble substances. They are dynamic lesions, regulated by complex immune mechanisms. Tachykinins are a family of neuropeptides characterized by the common C-terminal amino acid sequence -Phe-X-Gly-Leu-Met-NH2. One such tachykinin, substance P, has been reported to modulate immunologic responses. In this investigation, granulomas were examined for substance P. Granulomas were isolated from the livers of mice infected with murine schistosomiasis, and substance P was extracted. Immunoreactive substance P was detected by RIA. The authenticity of the molecule was confirmed by elution profile on HPLC. Immunoreactive substance P, identified by immunostaining, localized to eosinophils derived from collagenase-dispersed granulomas. Granulomas were then probed for expression of the gene for substance P (preprotachykinin). Preprotachykinin mRNA was localized to granuloma eosinophils by in situ oligonucleotide hybridization. It is concluded that substance P is present within the granuloma as a result of preprotachykinin production by eosinophils.

Animals↗
PubMed1988

Macrophages isolated from liver granulomas of murine Schistosoma mansoni synthesize predominantly TxA2 during the acute and chronic phases of infection.

Macrophages isolated from liver granulomas of mice infected with Schistosoma mansoni for 8 or 20 wk synthesize predominantly thromboxane A2 with smaller amounts of the PGE2 and PGI2. There is no physiologic production of leukotrienes, as determined by RIA and HPLC. Thromboxane A2 is the predominant arachidonic acid metabolite whether the cells are stimulated by a phagocytic stimuli such as zymosan or the exogenous substrates arachidonic acid and PGH2. These data indicate that the predominant arachidonate enzymatic activity in these cells is thromboxane synthase.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Gastrointestinal angiodysplasia in renal failure.

We identified angiodysplasia as a cause of gastrointestinal bleeding in 15 of 47 patients (32%) with chronic renal failure (CRF) treated with dialysis who were evaluated for upper or lower gastrointestinal hemorrhage during a 5-year period. Nine patients had lesions in the upper, four in the lower, and two in the upper and lower gastrointestinal tract. Ten patients with angiodysplasia experienced more than one bleeding episode during that time. Active hemorrhage from a vascular lesion was seen in nine patients (60%). Erosive gastritis and/or duodenitis was the second most common finding. These data confirm how frequent a cause of recurrent bleeding angiodysplasia is in patients with CRF undergoing dialysis.

Digestive System↗
PubMed1987

Modulation of granulomatous inflammation in murine schistosomiasis mansoni by enteric exposure to schistosome ova: in vitro characterization of a regulatory mechanism within the granuloma.

Enteric immunization with schistosome ova results in a diminished granulomatous response. This study explored a mechanism by which enteric immunization may decrease granuloma size. Granulomas from livers of acutely infected mice were dissociated and the dispersed cells were depleted of macrophages. As defined by a direct in vitro migration inhibition factor (MIF) assay, the macrophage-depleted cells, composed of lymphocytes and eosinophils, inhibited the migration of normal peritoneal exudate cells when exposed to soluble egg antigens. Anti-Thy 1.2 or -Lyt 1.1, but not -Lyt 2.1, treatment of these cells abrogated MIF activity. Next, mice were exposed enterically to eggs 4 weeks prior to sacrifice. Cells from granulomas isolated from these animals demonstrated no MIF activity unless treated with anti-Lyt 2.1. When granuloma cells from enterically immunized mice were mixed with those from unimmunized animals, MIF activity by the latter was abrogated. Treatment of cells from immunized mice with anti-Lyt 2.1 or -Thy 1.2, but not -Lyt 1.1 prior to mixing once again permitted MIF activity. These results suggest that the diminished granulomatous response induced by enteric immunization could be mediated by Lyt 2+ suppressor T cells. These suppressor cells may regulate the MIF activity of Lyt 1+ T lymphocytes residing within these lesions.

Animals↗
PubMed1987

Synthesis of angiotensins by cultured granuloma macrophages in murine schistosomiasis mansoni.

Components of the angiotensin system are present in granulomas of murine schistosomiasis mansoni. Angiotensins may have immunoregulatory function. Granuloma macrophages cultured for up to 3 days generated substantial angiotensin I (AI) and angiotensin II (AII) which appeared in the culture supernatants. Macrophage monolayers were incubated with 3H-labeled amino acids, and culture supernatants were extracted with acetone and analyzed by HPLC. Radiolabeled products eluted at times corresponding to those of authentic angiotensins. Immunoadsorption of angiotensins with angiotensin antisera removed reputed radiolabeled angiotensins from the supernatants. Treatment of the elution fraction corresponding to that of authentic AI with angiotensin-converting enzyme resulted in the generation of radiolabeled polypeptides which coeluted with authentic AII and His-Leu. Similar experiments conducted with nonadherent granuloma cells devoid of macrophages failed to demonstrate angiotensin production. These results suggest that granuloma macrophages can synthesize angiotensins.

Angiotensins↗
PubMed1987

Angiotensin II is chemotactic for a T-cell subset which can express migration inhibition factor activity in murine schistosomiasis mansoni.

In murine schistosomiasis mansoni, ova induce a delayed-type hypersensitivity, granulomatous response in which angiotensins are produced. Angiotensin II (AII) elicits a chemotaxis for splenic mononuclear cells derived from these infected animals. The effect of AII upon the migration of a T-lymphocyte subset was defined functionally to further delineate this observation. A chemotaxis chamber was developed that permitted collection of large numbers of viable cells which migrate in response to AII. In a direct migration inhibition factor (MIF) assay, MIF activity was demonstrated with 100-fold fewer chemotactically attracted cells as opposed to whole splenic leukocytes. The MIF activity was eliminated by treatment of the cells with anti-Lyt 1.1 or-Thy 1.2 serum and complement. This observation was particularly interesting since migrated and whole spleen cell populations comprised equal numbers of T cells. Incubation of spleen cells with AII prior to assay did not alter MIF activity. These findings suggest that AII is chemotactic for at least one important T-cell subset relevant to the granulomatous response.

Angiotensin II↗
PubMed1986

Chemotactic response of splenic mononuclear cells to angiotensin II in murine schistosomiasis.

Murine Schistosomiasis mansoni is a parasitic infection associated with a delayed-type hypersensitivity granulomatous reaction to the schistosome eggs. This reaction is characterized by the accumulation of mononuclear cells and other inflammatory cell types around the eggs. Granuloma macrophages produce angiotensin II (AII), which appears to have immunoregulatory function. By using an in vitro chemotaxis assay, this study demonstrated that AII is a chemotactic factor for splenic mononuclear cells derived from infected mice. The response was bimodal, with peak activities occurring at 10(-10) and 10(-6) M. AII was chemotactic for T lymphocytes, B lymphocytes, and a large population of unidentified mononuclear cells at the optimal chemotactic concentrations of the peptide. At high concentrations, AII was also chemotactic for phagocytic mononuclear cells. Sar1, ala8-AII, an analog of AII with antagonist activity, completely blocked AII-induced chemotaxis. A [3H]-AII binding assay revealed high-affinity specific binding on spleen cells. The binding was rapid, was dependent on radioligand concentration, and was reversible. These latter observations suggest that the chemotactic activity of AII for subpopulations of splenic mononuclear cells is mediated via AII receptors.

Angiotensin II↗
PubMed1986

The significance of angiotensin I converting enzyme in granulomatous inflammation. Functions of ACE in granulomas.

ACE is a carboxy-terminal peptidyl dipeptidase which can be produced by granuloma macrophages and possibly by other components of the granuloma. ACE activity is influenced by regulatory T cells. This enzyme may be important in mediating and/or modulating inflammation. One mechanism involves the generation of angiotensin II which can effect inflammatory reactions. Although unstudied, ACE may also be an important inactivator of bradykinin and various neuropeptides which in turn may participate in the immunoregulation of the granuloma. Thus, therapeutic strategies designed to alter ACE activity within granulomas may alter the size, composition and ultimate resolution of these lesions.

Animals↗
PubMed1986

Angiotensin II suppression of human mononuclear cell reactivity is associated with enhanced OKT8+ lymphocyte thymidine incorporation.

Recent evidence suggests that angiotensin II may participate in the regulation of inflammation. We previously reported that angiotensin II inhibits human peripheral blood mononuclear cell reactivity and acts directly on lymphocytes. These observations are again confirmed. In addition, purified OKT8+ but not OKT4+ T cell suspensions stimulated with phytohemagglutinin revealed increased thymidine incorporation when simultaneously cultured for 48 hours with angiotensin II. These findings suggest that angiotensin II may inhibit mononuclear cell thymidine uptake through stimulation of suppressor lymphocytes contained within the OKT8+ subpopulation.

Angiotensin II↗
PubMed1986

Serum antibodies from patients with Crohn's disease and from their household members react with murine lymphomas induced by Crohn's disease tissue filtrates.

Injection into athymic nude mice (nu/nu) of filtrates of Crohn's disease tissue produces lymphoid hyperplasia and lymphomas, which react with serum antibody from other patients with Crohn's disease. We examined for such antibodies in sera of 14 patients with Crohn's disease and 25 of their household members and compared results with sera from 36 healthy unselected controls and from 14 patients with ulcerative colitis and 19 of their household members. Sera from all patients with Crohn's disease and ulcerative colitis and household members were collected in Michigan, coded, and examined by an indirect immunofluorescence assay against two primary nu/nu lymphomas and one transmitted lymphoma produced by three Crohn's disease tissue filtrates. Seven patients with Crohn's disease had antibodies against antigen(s) in the Crohn's disease lymphomas. Seven household members of patients with Crohn's disease and no household members of patients with ulcerative colitis (P less than 0.05) reacted with Crohn's disease lymphomas. However, none of the patients with ulcerative colitis (P less than 0.01) and no control healthy subjects (P less than 0.005) demonstrated immunoreactivity against nu/nu lymphomas. None of the sera reacted with a control nu/nu lymphoma. Five household members who had positive assay results were first-degree blood relatives, and the other two were spouses of patients with Crohn's disease. These results suggest that a common environmental factor may be associated with Crohn's disease, that there is a familial association in Crohn's disease, and that nu/nu mice are an important model to study the pathogenesis of Crohn's disease.

Adult↗
PubMed1985

Effects of granuloma modulation induced by regulatory-T-lymphocyte activity on angiotensin II/III production by granuloma macrophages in murine schistosomiasis mansoni.

Angiotensins are produced by granuloma macrophages in murine Schistosoma mansoni. During the course of infection, granuloma undergo a T-cell-dependent process called modulation in which their maximal size decreases. This study was undertaken to establish whether angiotensin production by granuloma macrophages is altered by immunoregulatory lymphocytes. Granuloma macrophages from modulated lesions released and contained more angiotensin II/III (AII/III) and less angiotensin I (AI) than those from the acute infection. Captopril, a specific angiotensin-converting-enzyme (ACE) inhibitor, appreciably decreased AII/III produced by macrophages from modulated granulomas. Adoptive transfer of splenic T lymphocytes from chronically infected donors into acutely infected recipients altered angiotensin production by the granuloma macrophages in a manner similar to that seen in modulated lesions. However, no difference was detected in the capacity of granuloma macrophages from acutely or chronically infected mice to metabolize 125I-AI or -AII added to cell cultures. Similarly, captopril did not alter the metabolism of exogenously administrated angiotensins. These findings suggest that regulatory T lymphocytes influence the metabolism by granuloma macrophages of endogenously produced angiotensins at least in part by induction of macrophage ACE activity. However, the degradation of extracellular AI and AII may result from the activity of enzymes other than ACE which are not inducible by modulation.

Angiotensin II↗
PubMed1985

The effect of angiotensin II on human mononuclear cell reactivity: suppression of PHA-P-induced thymidine incorporation.

Recent evidence suggests that angiotensin II may participate in the regulation of inflammation. We therefore studied the effects of angiotension II on human peripheral blood mononuclear cell reactivity. Peripheral blood mononuclear cell suspensions stimulated with PHA-P revealed decreased thymidine incorporation when simultaneously cultured for 48 or 72 hours with angiotensin II. Experiments were next conducted to determine whether angiotensin II acted directly on lymphocytes. Complete monocyte depletion (greater than 99.5%) resulted in low PHA-P-induced reactivity which was still inhibited by the addition of angiotensin II. Purified (greater than 99.5%) lymphocytes incubated with angiotensin II prior to reconstitution of mixed mononuclear cell suspensions led to reduced PHA-P-stimulated thymidine incorporation. These findings suggest that angiotensin II can effect mononuclear cell uptake possibly through actions on the lymphocyte population.

Adult↗