Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Granulomas”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

[A study of epithelioid cell granulomas in transbronchial lung biopsy specimens of sarcoidosis patients--correlation between granulomas and clinical activity or chest X-ray lesions].

The 565 pulmonary tissue specimens taken from 155 sarcoidosis patients by transbronchial lung biopsy (TBLB) were studied by light microscopy. Particular attention was paid to the mean number and type of epithelioid cell granulomas, the mean number of giant cells, and the degree of lymphocyte cuffing, perigranulomal fibrosis, and granuloma confluence. The granulomas were divided into three types, hypertrophic, atrophic, and hyalinofibrous. In stage II and III patients, the mean number of granulomas and giant cells, the positive rate of hyalinofibrous granuloma, the relative proportion of the hyalinofibrous granuloma group, and the degree of fibrosis and confluence were significantly higher than those in stage O and I patients. The mean number of granulomas was related to the serum level of angiotensin converting enzyme and 67Ga uptake into lung parenchyma, but not to the cellular findings of bronchoalveolar lavage fluid (BALF). The lymphocyte count of BALF in the hypertrophic granuloma group was significantly higher than that in the atrophic and hyalinofibrous granuloma groups. CD4/CD8 ratio of lymphocytes in BALF was significantly lower in the hyalinofibrous granuloma group than in the other groups. In stage I patients, the resolution of intrathoracic lesions on chest X-ray was significantly more frequent in the atrophic granuloma group than in the hypertrophic granuloma group, 2 and 5 years after TBLB was performed. The pulmonary lesions had a tendency to persist for a long time in stage II and III patients with hyalinofibrous granuloma or granuloma confluence. Newly appearing pulmonary lesions showed hypertrophic granulomas as well as marked lymphocyte cuffing.

Adolescent↗
PubMed1985

Collagenase, elastase, and nonspecific protease production by vigorous or immunomodulated liver granulomas and granuloma macrophages/eosinophils of S mansoni-infected mice.

Schistosomiasis mansoni is characterized by granulomatous inflammations, deposition of collagen, and irreversible liver fibrosis. In chronic infections fibrosis is cumulative, while collagen synthesis and degradation are diminished. In the present study, we compared collagenase, elastase, and nonspecific neutral protease (NP) activities in isolated vigorous (8-week infection) and immunomodulated (18-20-week infection) liver granulomas. Enzyme activity was localized in the adherent macrophage (greater than 90% purity) and nonadherent eosinophil-rich (greater than 70% purity) cell fractions of the disaggregated granulomas. Collagenase levels were approximately two times higher in granuloma extracts and explant culture supernates of the vigorous as compared with the immunoregulated lesions. However, macrophages and eosinophil-rich cells derived from either type of granuloma secreted similar enzyme levels. Elastase and NP levels in granuloma extracts and secretions of adherent macrophage and eosinophil-rich cell populations were the same in vigorous or immunomodulated lesions but were significantly greater in vigorous granuloma culture supernates. In addition to active collagenase, trypsin activatable latent collagenase was also present in both types of granuloma extracts, explants and eosinophil-rich cell culture supernates. Latent elastase was also detected in granuloma extracts or explant supernates but was absent from secretions of granuloma cells. These results suggest that the presence of active neutral proteases within granulomas may play an important role in the regulation of tissue repair and remodeling during the fibrotic process.

Animals↗
PubMed1982

Experimental production of pulmonary granulomas; II. Age dependency and immune modulation of granuloma production.

Endobronchial instillation of Freund's complete adjuvant (FCA) induced epithelioid cell granulomas in the lungs of juvenile rabbits which had been kept free from contamination with the microbiol antigens. The granulomas were named "juvenile granulomas", because, unlike FCA granulomas in adult animals, prior immunization was unnecessary for their induction. The granulomas developed in several weeks with a peak at 14 weeks of age, after which the production decreased gradually. The rate of granuloma production seemed to vary with the acquisition of skin hypersensitivity to tuberculin (OT), suggesting that granuloma production, as well as skin hypersensitivity, is in the category of T-dependent immune reactions. In fact, T-generating lymphoid organs developed in parallel with the dermal and pulmonary reactions. Thus, juvenile rabbits at about 14 weeks of age are most susceptible to the microbial antigens. This susceptibility results in the unexpected production of immune granulomas in response to depot antigens at the site of instillation. The treatment of foetal or neonatal rabbits with FCA markedly suppressed granuloma production in juveniles but not in adults and did suppress but gradually enhanced the tuberculin skin reaction. It is suggested that generation of suppressor T cells is the cause of suppression of juvenile granuloma production.

Aging↗
PubMed1989

Granuloma formation by artificial microparticles in vitro. Macrophages and monokines play a critical role in granuloma formation.

To investigate the basic mechanisms of granuloma formation, in vitro granulomas were induced by culturing murine spleen cells in the presence of artificial microparticles. Large granulomas developed around dextran beads. The lesions were inducible by spleen cells from either normal mice or athymic nude mice. Minimal inflammation was produced around latex beads. The histologic features and time kinetics of granulomas in vitro. Culture supernatants of dextran induced granulomas contained high levels of interleukin-1 (IL-1) activity but not interleukin-2 (IL-2) or interleukin-4 (IL-4) activity. IL-1 activity was correlated with granuloma size. Additionally, granulomas were produced by culturing spleen cells in the presence of agarose beads coupled to recombinant IL-1 or recombinant tumor necrosis factor-alpha (TNF-alpha). Granulomatous lesions also were induced by macrophage-enriched populations in the presence of monokine-coupled beads. Adherent macrophages, but not nonadherent cells, were required for induction of granulomas in vitro. In contrast, very small lesions were seen when spleen cells or adherent cells were cultured in the presence of beads coupled to recombinant IL-2 or recombinant interferon-gamma (IFN-gamma). These results suggest that macrophages and monokines such as IL-1 and TNF-alpha play an essential role in granuloma formation in vitro.

Animals↗
PubMed1988

Direct evidence for granuloma-inducing activity of interleukin-1. Induction of experimental pulmonary granuloma formation in mice by interleukin-1-coupled beads.

Pulmonary granulomas were induced in BALB/c mice by the intratracheal injection of Sephadex G-50 and latex beads. Very large granulomas developed around Sephadex G-50 beads. Minimal inflammation was produced in mice given latex beads. Aqueous extracts prepared from pulmonary granuloma lesions induced in mice by Sephadex G-50 beads contained high levels of interleukin-1 (IL-1) activity but not interleukin-2 (IL-2) activity. IL-1 activity in the extracts correlated with granuloma size. In a subsequent step, large granulomas were induced by the intratracheal injection of Sepharose 4B beads coupled to fractions of the extracts containing IL-1 activity (ie, granuloma-derived IL-1) prepared from Sephadex G-50-induced granulomatous lungs. In addition, large granulomas were induced by the intratracheal injection of recombinant IL-1-coated Sepharose 4B beads. In contrast, very small granulomas were seen when IL-2-coated or plain Sepharose 4B beads were injected into mice. These results indicate that IL-1 participates in the induction and/or expression of granulomas.

Animals↗
PubMed1983

Granuloma formation and killing functions of granuloma in congenitally athymic nude mice infected with Blastomyces dermatitidis and Paracoccidioides brasiliensis.

We did this experiment to clarify the mechanism of granuloma formation and the killing functions of granuloma in nude mice against Blastomyces dermatitidis and Paracoccidioides brasiliensis infections. B. dermatitidis A-295 and P. brasiliensis B-1183 were the cultures used. Congenitally athymic nude (nu/nu) mice and their heterozygous (nu/+) littermates of BALB/c background were the test animals. From culture A-295, 0.1% and 1% cell suspensions (wet weight) were prepared and from culture B-1183 0.2% and 2% cells suspensions were prepared. Ten nu/+ and 10 nu/nu mice were allotted to each of four cell suspensions. For experimental blastomycosis each mouse was inoculated intravenously with 0.2 ml of the cell suspension of A-295 and for experimental paracoccidioidomycosis, with 0.15 ml of the cell suspension of B-1183. Two mice from each of the four groups were killed at 5, 8, 12, 18 and 25 days after inoculation, and histopathologic sections, stained with H&E or by PAS, were prepared from various internal organs. In the nu/nu mice inoculated with B. dermatitidis A-295 granuloma was formed in the brain tissue after the 12th day. However, mononuclear cells, which formed the granuloma, did not kill the fungal cells, and the fungal cells continued to multiply in the granuloma. On the other hand, in the heart, kidney and fat tissue, their histopathological findings after the 18th day were clumps of fungal cells with slight cell reactions. In these organs the exertion of cell-mediated immunity was necessary for granuloma formation against the fungal infection. In the nu/nu mice infected with P. brasiliensis B-1183, granuloma appeared in the brain and kidney after the 18th day and fungal cells continued to multiply within the granuloma as well as in those inoculated with culture A-295. These results show that the exertion of cell-mediated immunity plays an important role in the mouse's defense mechanisms against these fungal infections. We assume that the defense mechanisms of immunocompetent mice against B. dermatitidis or P. brasiliensis infection consist chiefly of two steps: in the first step phagocytosis by PMNs occurs and in the second step cell-mediated immunity enters into play.

Adipose Tissue↗
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↗
PubMed1978

Inhibitory effects of glucocorticoids on collagen synthesis by mouse sponge granulomas and granuloma fibroblasts in culture.

The basis for the glucocorticoid-mediated decrease in tissue collagen was studied in mouse granulomas and in primary granuloma fibroblast cultures. Injection of mice for 12 days with dexamethasone (0.35 mg/kg body weight) resulted in a 50--70% inhibition of collagen synthesis and accumulation in polyvinyl sponge-induced granulomas whereas total protein synthesis was inhibited by only about 25%. The decreased collagen content of the granuloma was accounted for by both a reduced fibroblast number and diminished synthesis per cell. Growth rates, total protein synthesis and collagen synthesis were the same in granuloma fibroblast cultures derived from control or steroid-treated mice. However, addition of 3.10(-7) M hydrocortisone to the culture medium caused a 30--50% inhibition of both collagen and non-collagen protein synthesis in firbroblasts from either source. These inhibitory effects were dose- and time-dependent with a lag time of 12--24 h. Prolyl hydroxylase activity was reduced both in sponge granulomas from glucocorticoid-treated mice and in hydrocortisone-treated fibroblast cultures. However, protein synthesis was inhibited to the same extent as the inhibition of prolyl hydroxylase activity and there was no effect on peptidyl prolyl hydroxylation. These results indicate that the glucocorticoid-induced reduction of collagen synthesis and accumulation observed in mouse granulomas and primary granuloma fibroblast cultures is not specific for this protein. Furthermore, glucocorticoid-induced inhibition of collagen synthesis cannot be attributed to underhydroxylation of collagen prolyl residues.

Animals↗
PubMed1989

Generalized granuloma annulare: histopathology and immunopathology. Systematic review of 100 cases and comparison with localized granuloma annulare.

Some form of collagen alteration (necrobiosis) was observed in 53% of patients with generalized granuloma annulare and in 79% of patients with localized granuloma annulare. Fragmentation of collagen bundles was the most common single type of collagen abnormality in both groups. Collagen sclerosis, accompanied by a strong palisading pattern of histiocytes, was more frequent in localized granuloma annulare. Results of microdroplet lipid staining were positive in 80% of annulare cases and 39.3% of nonannulare cases of generalized granuloma annulare. Inflammatory cells were confined to peripheral perivascular lymphocytes; bandlike granuloma below the epidermis was observed. Positive results of direct immunofluorescence tests in 12 of 23 patients with generalized granuloma annulare suggested that fibrin deposition in areas of altered collagen is less frequent in the generalized than in the localized form, a possible reflection of the lower rate of histologic collagen alteration in that group. Lymphohistiocytic granuloma with various degrees of collagen degeneration, microdroplet lipid accumulation, and mucin deposition form the basic pathologic description of granuloma annulare.

Collagen↗
PubMed1977

[Paper disk granuloma method for experimental granuloma in rats (author's transl)].

The paper disk granuloma (PDG) method is a newly devised procedure for the screening of antiinflammatory drugs and was compared with the cotton pellet (CP) method. Results obtained were as follows; in the CP method, formation of granuloma was observed on the 1st day after the implantation of CP. On the 3rd day, maximum weight, protein and nucleic acids in granuloma were observed. The granuloma produced by PDG method was too small to collect on the 1st day. Weight and protein content of granuloma reached the peak on the 2nd or 3rd day. With respect to nucleic acids, maximum amounts were found on the 6th day. The incorporation of 3H-uridine into RNA was increased in the early stage of the formation of granuloma in both methods. The maximum incorporation of 3H-thymidine into DNA was noted on the 2nd day in CP method, and on the 3rd day in PDG method. Development of granuloma in the PDG method was different from that in CP method with respect to the synthesis of DNA. Antigranuloma action of fluocinolone acetonide (FA) was more marked in the PDG method than in the CP method, suggesting that the PDG method is more sensitive for screening of antiinflammatory drugs. Granuloma produced by the PDG method was also prevented and therapeutically suppressed by certain non-steroidal antiinflammatory drugs. ED50 values of applied FA, phenylbutazone, and 3-o-phthaloxy glycyrrhetinate were 27 microgram/kg, 91 mg/kg, and 66 mg/kg, respectively.

Absorption↗
PubMed1989

The molecular basis of granuloma formation in schistosomiasis. III. In vivo effects of a T cell-derived suppressor effector factor and IL-2 on granuloma formation.

Granuloma formation in schistosomiasis is characterized by the formation of a large lesion in acutely infected animals which subsequently decreases in size as disease progresses into the chronic phase. These in vivo studies confirm and extend previous in vitro observations on the regulation of granulomatous hypersensitivity by a T cell-derived suppressor effector factor (TseF). TseF regulation of granuloma formation in vivo and DTH are shown to be both antigenically and genetically restricted. This suppression is accompanied by a suppression of the ability of cells derived from TseF recipients to function in an in vitro assay of granuloma formation. Antigenic recognition, defined by cellular proliferation in response to antigenic stimulation, is uneffected by TseF administration. Administration of IL-2 reduces TseF function in acutely infected mice and results in increased liver granuloma size. However, the ability of cells derived from these animals to form granulomas in vitro is uneffected. Cells obtained from chronically infected IL-2 recipients do not produce TseF in vitro and granuloma size is increased in these animals. Animals receiving both IL-2 and TseF continue to demonstrate decreased granuloma formation, indicating that IL-2 does not effect the ability of preformed TseF to function. These observations suggest that TseF modulates granuloma formation in vivo and may interact with IL-2 in a dynamic process which determines the intensity of the granulomatous response.

Adjuvants, Immunologic↗
PubMed1990

[Experimental hypersensitivity pneumonitis and enhancement of granuloma formation by low dose irradiation with increased interleukin-1 activity of granuloma in genetically low responder mouse (C3H)].

Possible enhancing effects by low dose total body irradiation on pulmonary granuloma formation induced by intratracheal injection of ovalbumin-coupled beads in low responder C3H mouse were studied. The low dose (3.5 Gy) irradiation increased the size of granuloma in low responder C3H mouse as large as the granuloma formed in high responder C57BL/10 mouse. The resolution of granuloma which usually disappeared within 9 days was also prolonged by the irradiation. Increase in IL-1 activity of lung extracts but not IL-2 activity was parallel to the enhancement of granuloma formation and/or the delayed resolution of granuloma. These results indicated that the radiation-sensitive cells might regulate IL-1 producing cell, possibly macrophages which made pulmonary granuloma.

Alveolitis, Extrinsic Allergic↗
PubMed1992

[The dynamics of antigen and antibody in Schistosoma japonicum egg granuloma and its relationship with the granuloma response].

Synchronous Schistosoma japonicum egg granuloma in the lung of mouse model and PAP (peroxidas-anti-peroxidase) technique were employed to study the dynamics of antigen and antibody in the egg granuloma of S. japouicum and its relationship with the granuloma formation. The granulomatous response began on the 3.5 day after egg injection and increased to the maximal size at the 4th week. Lymphocyte populations and macrophage comprised an important part of lesions during the time of acute granulomatous response (7-28 day). Using PAP staining, the SEA within egg could be detected at high level on the first day after egg injection and then declined gradually. On the contrary, the SEA around egg was minimal at the first week and increased to the peak at the 4th week, then decreased gradually. No antibody could be detected throughout the experimental period (35 days). The results suggested that 1) the antigen of Schistosoma egg is the essential factor for the granuloma formation. 2) S. japonicum egg granuloma could be formed in unsensitized mouse. 3) The mechanism of egg granuloma formation of S. japonicum is similar to that of S. mansoni.

Animals↗
PubMed2026

Granuloma dual RNA-seq reveals composite transcriptional programs driven by neutrophils and necrosis within tuberculous granulomas.

Mycobacterial granulomas lie at the center of tuberculosis (TB) pathogenesis and represent a unique niche where infecting bacteria survive under nutrient-restricted conditions and in the face of a host immune response. The granuloma's necrotic core, where bacteria reside extracellularly in humans, is difficult to assess in many experimentally tractable models. Here, using necrotic mycobacterial granulomas in adult zebrafish, we develop dual RNA sequencing (RNA-seq) across different host genotypes to identify the transcriptional alterations that enable bacteria to survive within this key microenvironment. Using pharmacological and genetic interventions, we find that neutrophils within mature, necrotic granulomas promote bacterial growth, in part through up-regulation of the bacterial devR regulon. We identify conserved suites of bacterial transcriptional programs induced only in the context of this unique necrotic extracellular niche, including bacterial modules related to K+ transport and rpf genes. Analysis of Mycobacterium tuberculosis strains across diverse lineages and human populations suggests that granuloma-specific transcriptional modules are targets for bacterial genetic adaptation in the context of human infection.

Animals↗
PubMed1984

Delayed type hypersensitivity granuloma formation around Schistosoma mansoni eggs in vitro. IV. Granuloma formation in human schistosomiasis.

Peripheral blood mononuclear cells, obtained from 42 school-age Egyptian children, were isolated on Ficoll-hypaque density gradients and assayed for granuloma formation. A granuloma index (G.I.) which classified the cellular reactions to Schistosoma mansoni eggs was determined for each patient. Morphologic criteria to assess the cellular reactivity included cell adherence, blast cell transformation, cell migration, and circumoval accumulation of inflammatory cells around the egg. The difference between the mean granuloma index of uninfected controls (G.I. = 1.25 +/- 0.04) and infected patients (G.I. = 1.58 +/- 0.05) was statistically significant (P less than 0.01; Student's t-test). There was no correlation between the granuloma indices and infection intensities determined by quantitative egg counts or between anti-major serological antigen antibody titers. These data demonstrate the feasibility of studying granulomatous hypersensitivity in human schistosomiasis utilizing an in vitro model of granuloma formation and peripheral blood cells.

Adolescent↗
PubMedDate not supplied

Ultrastructural characteristics of macrophages in dermal leprosy granulomas: macrophages in leprosy granulomas.

The characteristics of the cells of mononuclear phagocyte series (MPS) in the dermal granulomas of tuberculoid and lepromatous leprosy were studied by elereron microscopy. In the tuberculoid granulomas, majority of the cells of MPS (epithelioid cells) showed a distinct appearance. They were seen in close association with a large number of activated lymphocytes. The cells of MPS had a prominent nucleus. Their cytoplasm contained mainly rough endoplasmic reticulum, developed golgi and was free of M. leprae or its products. In contrast, the cells of MPS (macrophages) in lepromatous leprosy had a large nucleus. Their cytoplasm contained mainly whole M. leprae organisms/its phagocytosed products and rough endoplasmic reticulum. There was paucity of lymphocytes in these granulomas. These observations support the view that the cells of MPS in the tuberculoid granulomas may be secretory while those in the lepromatous granulomas were phagocytic.

Granuloma↗
PubMed1978

The Churg-Strauss granuloma: cutaneous, necrotizing, palisading granuloma in vasculitis syndromes.

The cutaneous, necrotizing, palisading granuloma (Churg-Strauss granuloma) was observed on histopathologic study of skin specimens from seven patients. Two patients had Wegener's granulomatosis and one patient each had allergic granulomatosis, limited Wegener's granulomatosis, bacterial endocarditis, systemic lupus erythematosus, and rheumatoid arthritis. The microscopic picture consists of extravascular, palisading, dermal granuloma. The center of the granuloma consists of basophilic fibrillar necrosis in which linear bands of destroyed tissue are interspersed with masses of polymorphonuclear leukocytes and leukocytoclastic debris. This necrotic leukocytic mass is surrounded by histiocytes and some lymphocytes. The clinical lesions are symmetric, erythematous papules or nodules on the extremities. The histopathologic picture of the Churg-Strauss granuloma is unique and, as demonstrated in these cases, indicates the presence of systemic vasculitis.

Granulomatosis with Polyangiitis↗
PubMed1986

Linoleic and dihomo-gamma-linolenic acids modulate granuloma growth and granuloma macrophage eicosanoid release.

We have already demonstrated that arachidonic acid (AA) inhibits carrageenin-induced granuloma growth in vivo and that this effect is related to an increase in prostaglandin E2 formation. As prostaglandin E1 has been shown to be more effective in inhibiting granuloma growth than prostaglandin E2 we investigated the effect of linoleic acid (LA) (18:2 omega 6) and dihomo-gamma-linolenic acid (DHGLA) (20:3 omega 6), potential precursors of prostaglandin E1, in this model. LA and DHGLA inhibited the development of carrageenin-induced granulomas in the rat when injected locally. Both fatty acids (FA) stimulated the release of prostaglandin (PG) E1 from granuloma macrophages (M phi) in vitro, DHGLA being most effective. LA had little effect on the release of PGE2, 6 keto PGF1 alpha, the stable product of prostacyclin (PGI2) or thromboxane (Tx) B2, the stable metabolite of TxA2. DHGLA had no effect on the release of 6 keto PGF1 alpha, but inhibited PGE2 and, to a lesser extent, TxB2 synthesis.

Alprostadil↗