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D L Boros

Publications and source records attributed to D L Boros.

At least 73 records · Page 4Linked to original sources
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

Modulation of granulomatous hypersensitivity. IV. Immunoglobulin and antibody production by vigorous and immunomodulated liver granulomas of Schistosoma mansoni-infected mice.

The interlesional production of immunoglobulins and SEA-specific antibodies was examined in vitro in cultured hepatic granulomas isolated from Schistosoma mansoni-infected mice. Vigorous lesions of 8-wk and immunomodulated lesions of 20-wk infected mice were cultured in serum-free medium for 48 hr; the supernatant fluid was concentrated, dialyzed, and tested for immunoglobulins by immunodiffusion. Whereas cultures of vigorous granulomas contained only IgG1, those of immunomodulated lesions yielded IgG1, IgG2a, IgG2b, IgG3, and IgA immunoglobulins. Both types of lesions incorporated 14C-labeled leucine into IgM and IgG class immunoglobulins thus proving intralesional synthesis. The immunoglobulins also had specific anti-SEA activity proven by passive hemagglutination and in vivo PCA test. The kinetics of SEA-specific IgM and IgG antibody-forming granuloma lymphocytes was examined by the plaque assay after the dispersal of the lesions. At 8 wk of the infection the number of IgM antibody-producing lymphocytes was low and that of IgG was negligible. In subsequent weeks both IgM and IgG antibody-forming cells increased in numbers. The IgM producer cells peaked at 12 to 16 wk and by 32 wk they dropped to barely detectable levels. The IgG antibody-producing lymphocytes peaked in numbers in the immunomodulated lesions at 20 wk and also disappeared by 32 wk. The kinetics of the granuloma lymphocytes as well as the magnitude of their response differed from those of splenic cells. Intralesional antibody production may promote antigen sequestration, complex formation, and occasional tissue injury. The participation of locally produced antibodies in the modulation of the granulomatous inflammatory response remains to be established.

Animals↗
PubMed1982

Tumoricidal macrophages isolated from liver granulomas of Schistosoma mansoni-infected mice.

In murine schistosomiasis, inflammatory macrophages (M phi) are a major cell type of the granulomata that encase eggs of the tropical helminth Schistosoma mansoni as they are deposited in the liver by adult worm pairs. The granulomatous response is vigorous during acute infection (8 wk) and spontaneously undergoes immunomodulation during chronic infection (20 wk). Inflammatory M phi isolated from liver granulomas of 8 and 20-wk schistosome-infected CBA/J mice were assessed for their cytolytic potential. Macrophages from vigorous liver granulomas displayed significant cytolytic activity against 3 mammary tumor lines of strain BALB/cfC3H origin, while leaving untransformed embryo fibroblasts relatively unharmed. The cytolytic activity of inflammatory M phi from immunomodulated lesions was markedly less than that of cells from vigorous lesions at equivalent effector to target (E:T) cell ratios. Granuloma cell preparations depleted of the inflammatory macrophage component were marginally cytolytic at the higher E:T cell ratio; supernatant fluids from cultured inflammatory M phi-enriched cell preparations possessed no tumoricidal activity. The cytolytic potential of the vigorous granuloma M phi was lost subsequent to prolonged in vitro culture. We conclude that inflammatory M phi in S. mansoni egg-elicited granulomas are sufficiently activated to lyse allogeneic tumor cells. The degree of activation appears to correlate directly with the intensity of the granulomatous response.

Acute Disease↗
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↗
PubMed1981

Modulation of granulomatous hypersensitivity. II. Participation of Ly 1+ and Ly 2+ T lymphocytes in the suppression of granuloma formation and lymphokine production in Schistosoma mansoni-infected mice.

The regulatory mechanism(s) active in the spontaneous suppression of parasite egg-induced granulomatous response was analyzed in Schistosoma mansoni-infected mice. A single injection of cyclophosphamide (CY) given to chronically infected mice with diminished granulomas and impaired ability to produce MIF restored the enhanced granulomatous response and lymphokine production by spleen cells. Drug-treated animals also showed a rise in the level of circulating anti-egg antigen antibody. After CY treatment, spleen cells were still capable of adoptively suppressing the vigorous granulomatous response and MIF production in acutely infected recipients. Adoptive suppression, however, was abrogated when spleen cells of chronically infected mice were pretreated with anti-Lyt 1.1 alloantiserum and C before transfer. Based on the present and previous observations, it is proposed that the modulated granulomatous inflammatory response in mice with chronic infection is maintained by a dynamic equilibrium between effector and regulator lymphocytes. Although the inflammation is maintained by Ly 1+ Ia- TDH cells, the intensity of the response is regulated by Ly 1+ Ia+ TH, Ly 2+ Ia+ Ts and possibly a putative precursor population of lymphocytes.

Animals↗
PubMed1980

Regulation of granulomatous inflammation in murine schistosomiasis. In vitro characterization of T lymphocyte subsets involved in the production and suppression of migration inhibition factor.

Host granulomatous inflammation in murine schistosomiasis mansoni is a T cell-mediated immune response, which, at the chronic stage of the disease, undergoes T suppressor lymphocyte-dependent modulation. In the present study this phenomenon was further analyzed in vitro. Spleen cells of mice undergoing modulation (20 wk of infection) when mixed with spleen cells of animals exhibiting vigorous granulomatous responses (8 wk of infection) abrogated in vitro migration inhibition factor (MIF) production by the latter. Characterization of the delayed-type hypersensitivity T lymphocytes involved in lymphokine production showed that they belonged to the Lyt-1+ subset and did not express I region-encoded antigens. In contrast, T lymphocytes involved in the suppression of MIF activity belonged to the Lyt-2+ subpopulation of cells, which expressed I-J- and I-C-subregion determinants. These results suggest that the modulation of the granulomatous hypersensitivity response in mice is the result of T-T cell interaction with subsequent regulation of inflammatory lymphokine production.

Animals↗
PubMed1980

Etiology of the liver granulomatous response in Schistosoma mansoni-infected athymic nude mice.

The effect of schistosome infection on the presence and maturation of splenic T lymphocytes in C3H/HeN nu/nu and nu/+ mice was examined. Spleens of uninfected nu/nu mice contained very low numbers (u to 2%) of T lymphocytes. This percentage did not increase throughout the 10 weeks of the infection. Spleens of uninfected nu/+ littermates contained 28.8% T cells, which decreased to 15.0% by week 10 of the infection. Similarly, whereas spleen cells of normal or infected nu/nu mice were nonresponsive to concanavalin A, the initial high response of nu/+ mice gradually diminished. Both nu/nu and nu/+ spleen cells responded well to lipopolysaccharide initially, but by 10 weeks their responsiveness declined. Sera of five infected nu/nu mice contained no antibodies to egg antigens, and one had a low titer (log2 5.0). In contrast, the mean titer of sera from six nu/+ mice was log2 10.7 Nu/+ mice had typical florid lesions, but nu/nu mice mounted sparse granulomatous reactions around eggs in the liver without evidence for hepatocellular damage. Dispersed liver granulomas of nu/nu mice contained 1.2% T and 20.3% B lymphocytes. Lesions of nu/+ mice contained 12.9% T and 18.4% B cells. Eighty percent of the macrophages from nu/nu and nu/+ granulomas displayed high density/avidity Fc receptors. Production of migration inhibition factor-active lymphokine by liver granulomas and spleens of schistosome-infected nu/nu mice is suggestive of the immune role of B cells in the granulomatous inflammation.

Animals↗
PubMed1980

The effect of splenectomy on the pathophysiology and egg-specific immune response of Schistosoma mansoni-infected mice.

Splenic involvement in murine schistosomiasis mansoni is manifested by splenomegaly, hyperplasia of the lymphoid and mononuclear phagocytic elements, and strong immune responses of splenic lymphocytes to schistosome antigens. In the present study, groups of Schistosoma mansoni-infected mice were splenectomized or sham treated at 1, 4, and 8 weeks of the infection, and at 12 weeks changes in pathophysiology, humoral, and granulomatous responses as well as liver fibrosis were examined. Splenectomy had no influence on the body and liver weight or portal presure of the infected mice. Mice which underwent splenectomy at 8 weeks developed anemia. Whereas splenectomy performed at 8 weeks of the infection did not affect the anti-schistosome egg antigen humoral response of the animals, it caused significant enhancement in the liver granulomatous reaction. Increased granuloma size did not result in a concomitant increase in the extent of liver fibrosis as measured by hydroxyproline content. It is concluded that the spleen may play an important role in the immunoregulation of the egg-specific granulomatous inflammatory response.

Animals↗
PubMed1979

Population dynamics of T and B lymphocytes in the lymphoid organs, circulation, and granulomas of mice infected with Schistosoma mansoni.

The T and B lymphocyte composition of the lymphoid organs, peripheral blood, and hepatic granulomas was determined in mice lightly infected with Schistosoma mansoni. Apart from an increase of circulating B cells, no change was seen in the distribution of lymphocytes prior to oviposition. Thereafter (8-20 weeks), a pronounced trend toward increased B and increased T cell percentages occurred throughout the organs. This effect was largely due to marked increases in the B cell population which outweighed increases of T cells occurring at 8 and 16 weeks. By the late chronic period (32 weeks), an overall normalization of percentages was observed due to declining B and/or increasing T cell numbers. Hepatic granulomas also showed notable compositional changes. At the time of maximum granulomatous response (8 weeks), the lymphocyte population of these lesions consisted primarily of T cells. Subsequently, during the time of modulated granuloma formation (12-32 weeks), B-cells became a significant component, comprising 10% of the granuloma cell population. The appearance of B cells within granulomas may indicate that they play a role in modulating granulomatous hypersensitivity.

Animals↗
PubMed1979

Modulation of granulomatous hypersensitivity. I. Characterization of T lymphocytes involved in the adoptive suppression of granuloma formation in Schistosoma mansoni-infected mice.

The cellular basis of the spontaneous modulation of the granulomatous response to schistosome eggs was analyzed in mice infected with Schistosoma mansoni. Spleen cells of 20 or 32 week-infected mice undergoing modulation, when transferred to 6 week-infected recipients, suppressed the maximal granulomatous response at 8 weeks. Suppression of both naturally forming asynchronous liver and synchronously induced lung lesions was achieved. Specificity of this effect was demonstrated by the suppression of egg granulomas but not antigen-coated bead granulomas developing simultaneously in the lungs of cell recipients. Further characterization showed that suppression was abrogated by pretreating transferred cells with either anti-Thy 1.2 or anti-Iak alloantisera and C. Transfer of macrophage-depleted or fractionated T and B spleen cells confirmed that T cells alone transferred suppression. Moreover, an Ia antigen-bearing (Ia+) subpopulation of T cells was required in the transferred suppression. Moreover, an Ia antigen-bearing (Ia+) subpopulation of T cells was required in the transferred population. An examination of T cells obtained from isolated, dispersed lung granulomas from control and adoptively suppressed mice revealed an increased proportion of Ia+ cells in the latter. It is suggested that Ia+ T cells may be involved in the local modulation of the granulomatous response.

Animals↗
PubMed1979

Fc-receptor-bearing macrophages isolated from hypersensitivity and foreign-body granulomas. Delineation of macrophage dynamics, fc receptor density/avidity and specificity.

Foreign-body and delayed hypersensitivity granulomas were induced in mice; and the dynamics of macrophages isolated from dispersed, 1--4-week-old lesions was delineated. The size and histologic complexity of the lesions increased as shown: adjuvant greater than schistosome egg greater than methylated bovine serum albumin greater than bead. Esterase staining, spreading on glass, and the percentage of Fc-receptor--bearing macrophages present in the various granulomas reflected the same gradient. The Fc receptors were examined by rosetting with rabbit-antibody--SRBC complex (EA). Whereas more than 90% of the population of macrophages of the dermal adjuvant granuloma contained undiminished numbers of receptor-bearing macrophages throughout the 4 weeks, the percentage of macrophages that displayed receptors in pulmonary foreign-body (40%) and delayed hypersensitivity granulomas (70%) peaked at 1 week and subsequently declined. The EA rosetting of the foreign-body and delayed hypersensitivity granuloma macrophages was strongly inhibited by monomeric IgG2a-specific and weakly by aggregated IgG2b-specific mouse myeloma proteins. Also, macrophages of the delayed hypersensitivity granulomas rosetted in higher percentages with SRBCs coupled with monomeric IgC2a than with those coupled with aggregated IgG2b myeloma proteins. Macrophages of the foreign-body lesion did not react with aggregated IgG2b--SRBC. Rosetting with monomeric IgG2a--SRBC or aggregated IgG2b--SRBC could not be cross-inhibited by the myeloma proteins. Both the monomeric IgG2a--SRBC and aggregated IgG2b--SRBC complexes were readily phagocytized. Trypsin treatment of the macrophages inhibited rosetting with EA or myeloma-protein--coupled SRBCs. The display of Fc receptors on the granuloma macrophages seems to be related to the etiology of the lesion and the intensity and duration of the inflammatory reaction.

Animals↗