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PubMed1988

Actinic granuloma (O'Brien).

Twelve cases of actinic granuloma (O'Brien) are reported. It is concluded that actinic granuloma is a specific disease characterized by clinical lesions indistinguishable from granuloma annulare, but occurring on solar damaged skin. Histologically, elastic tissue is destroyed by the granulomatous process in actinic granuloma, but not in granuloma annulare. It would appear that actinic granuloma, granuloma multiforme, necrobiosis lipoidica of the face and scalp (Wilson-Jones) and Miescher's granuloma of the face (Mehregan and Altman) are the same disease.

Adult↗
PubMed2006

RANKL in human periapical granuloma: possible involvement in periapical bone destruction.

OBJECTIVES: The cytokine receptor activator of nuclear factor kappaB-ligand (RANKL) has been involved in both the physiological and pathological regulation of osteoclast life span and bone metabolism. Periapical granuloma is a periradicular lesion characterized by periapical bone destruction. The aims of this study were to associate the RANKL mRNA levels to periapical granulomas using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to determine the specific cell involved in RANKL synthesis. METHODS: In eight periapical granuloma and eight periodontal ligament samples from periodontally healthy volunteers, RANKL mRNA was detected by real-time RT-PCR. Expression of RANKL on infiltrate leukocytes was further investigated by flow cytometry in six periapical granulomas. RESULTS: Receptor activator of nuclear factor kappaB-ligand mRNA levels were higher in periapical granulomas than in healthy periodontal ligament as its RANKL mRNA cycle threshold (Ct) and DeltaCt were significantly lower than that of controls (33.07 +/- 1.24 vs 36.96 +/- 1.69 and 11.58 +/- 3.02 vs 15.60 +/- 3.31, respectively). A 16.2-fold (2.0-131.6) higher RANKL gene expression was detected in the granulomas compared with the control tissues. We determined by flow cytometry that lymphocytes were the predominant leukocyte cells (53.31%), and monocytes and dendritic cells were the main RANKL synthesizers in granuloma lesions. CONCLUSIONS: These data indicate that monocytes synthesized RANKL in periapical granulomas and suggest that RANKL is involved in bone loss associated with periapical lesions.

Adolescent↗
PubMed1993

In vitro granuloma formation by spleen cells treated with psoralen plus long-wave ultraviolet radiation.

In vitro granulomas are induced by culturing murine spleen cells with artificial microparticles, dextran beads. In the presence of 0.5 microgram/mL 8-methoxypsoralen, UVA radiation (0.2-2.0 J/cm2) suppressed granuloma formation in a UVA dose-dependent manner. The doses of PUVA did not affect the cell viability as assessed by trypan blue exclusion. The time course of granuloma formation in 0.5 J/cm2 PUVA-treated cells was similar to that of normal spleen cells, with a maximum granuloma index at day 3 of culture, although a 49-63% suppression of granuloma formation was observed. PUVA-treated, nonadherent cells produced the same granuloma index when cultured with normal adherent cells. In contrast, a smaller granuloma index was observed in PUVA-treated adherent cells even when they were cultured with normal nonadherent cells. These data suggest that PUVA alters macrophages, resulting in the suppression of granuloma formation in vitro.

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↗
PubMed1989

Schistosomal egg granuloma-derived fibroblast-stimulating factor is apparently distinct from interleukin-1.

We have previously reported that egg granulomas isolated from livers of Schistosoma mansoni-infected euthymic mice in vitro elaborate a factor(s) that stimulates a variety of fibroblast responses including fibroblast proliferation and enhanced synthesis of extracellular matrix proteins. We have postulated that these factors play a role in the pathogenesis of hepatic fibrosis in schistosomiasis mansoni. Serum-free supernatants from egg granuloma cultures also stimulate thymocyte proliferation in an assay that defects interleukin-1 (IL-1). Thymocytes and fibroblasts are stimulated to proliferate by the same fractions of egg granuloma culture supernatant separated by gel filtration, isoelectric focusing, and ion-exchange chromatography. This suggested that granuloma-derived IL-1 is responsible for the observed fibroblast stimulation. Here we report that the ability of granuloma culture supernatants to stimulate the IL-1-sensitive D10.G4.1 cells but not fibroblasts is removed by treatment with immobilized anti-IL-1 antibody. We also observed that dialyzed culture supernatants from egg granulomas obtained from infected congenitally athymic (nude) mice also stimulate fibroblast proliferation. Treatment with anti-IL-1 antibody did not abrogate this response. In contrast to our experience with egg granulomas isolated from euthymic mice, IL-1- and fibroblast-stimulating activity could be separated by gel filtration and isoelectric focusing. We conclude that the fibroblast growth-stimulating activities elaborated by egg granulomas from S. mansoni-infected euthymic and athymic mice may be different but both appear to be distinct from IL-1.

Animals↗
PubMed1991

Isolated hepatic granulomas from mice infected with Schistosoma mansoni contain nerve growth factor.

Nerve growth factor (NGF) is a neurotrophic factor essential for the development and maintenance of specific neuronal cell populations. In addition, NGF has biological effects on inflammatory cells. The aim of this study was to determine whether NGF is present in chronic inflammation, using isolated hepatic granulomas from mice infected with Schistosoma mansoni as the model. The schistosome granuloma is a complex T-cell-mediated immune response to the egg. Intact granulomas were isolated from the livers of infected mice and examined for the presence of NGF. In homogenized granuloma samples, radioimmunoassay and immunoblotting analyses detected an immunoreactive NGF that had the same molecular mass as that of purified murine NGF (13 kDa). Isolated granulomas cultured in vitro released soluble factor(s) with NGF-like neurite-promoting activity in a rat pheochromocytoma (PC12) bioassay. This activity was partially inhibited by a blocking anti-NGF antibody. There were two potential sources of this NGF-like neurite-promoting activity, either the schistosome egg or the host inflammatory response. Since neither isolated eggs nor soluble egg antigen had neurite-promoting activity, the inflammation was the source of this activity. The inability of the anti-NGF antibody to inhibit completely the granuloma-induced neurite outgrowth in the bioassay signifies that NGF is not the only neurotrophic factor present in these granulomas. The presence of NGF within the granulomas may indicate that NGF has a role in the granulomatous response.

Animals↗
PubMed1994

Cloning of TH0- and TH2-type helper lymphocytes from liver granulomas of Schistosoma mansoni-infected mice.

The pathological manifestations of schistosomiasis mansoni are primarily induced by circumovum hepatic granuloma formation and fibrosis. The growth and modulation of the granulomas are regulated by T lymphocytes and their products. In the present study, we isolated T-lymphocyte clones from lesions at the acute and chronic stages of murine infection. All of the T-cell clones were characterized by immunofluorescence as CD4+CD8- helper cells. Three T-cell clones derived from vigorous granulomas produced interleukin 2 (IL-2), IL-4, and gamma interferon (IFN-gamma) and were therefore classified as TH0-type T lymphocytes. Of the three clones derived from immunomodulated lesions, two produced IL-2 or IL-4 and/or IFN-gamma (TH0 type) and the other one did not produce IFN-gamma but did produce IL-4 and was therefore characterized as a TH2-type helper clone. The clones were further characterized by their responsiveness to soluble egg antigen fractions. The acute infection-derived clones responded to the lower-molecular-mass (60- to 66-kDa and 25- to 30-kDa) fractions, whereas the immunomodulated-granuloma-derived clones responded to the 60- to 66-kDa and higher-molecular-mass (70- to 90-, 93- to 125-, and > 200-kDa) fractions. Upon adoptive transfer into naive mice, both the TH0- and TH2-type clones were capable of inducing granuloma formation of similar magnitude around antigen-coated beads and/or freshly isolated parasite eggs. The present study revealed the presence of TH0-type precursor helper cells within the liver granulomas. The findings underscore the complexity of the granulomatous response at the T-cell level and demonstrate that both TH0- and TH2-type granuloma lymphocytes play a role in parasite egg-induced granuloma formation.

Animals↗
PubMed1995

Suppressive effect of interleukin-4 neutralization differs for granulomas around Schistosoma mansoni eggs injected into mice compared with those around eggs laid in infected mice.

The principal pathological manifestation of murine Schistosoma mansoni infection is the egg-induced granuloma. Synchronous pulmonary granulomas forming around intravenously injected schistosome eggs are widely used to study the immunopathology of schistosomiasis. A number of anticytokine antibody treatments have a remarkable effect in modulating granulomas in this model but little effect on the size of hepatic granulomas around laid eggs during experimental infection. To examine this discrepancy, we examined the effects of anticytokine antibodies on liver and lung granulomas around injected eggs and around eggs laid during infection in both locations. Anti-interleukin-4 (IL-4) treatment greatly reduced the volume of granulomas around eggs injected into the liver via the portal vein and around eggs injected into the lung via the tail vein. On the contrary, granulomas around eggs laid by worms in either the liver or the lung during the course of infection were not significantly decreased in size by anti-IL-4 treatment. Thus, site is not important for the disparate effects of anti-IL-4 in granuloma formation around injected versus laid eggs. This effect is seen in naive and sensitized animals and is most probably due to differences in the quality of injected eggs versus those laid in situ by the worms.

Animals↗
PubMed1994

Role of lymphatic drainage on the development of Calmette-Guérin bacillus-induced granulomas in the hamster.

The influence of lymphatic drainage on Calmette-Guérin bacillus (BCG)-induced granulomas was investigated by comparing the time course of granuloma formation in two sites: the hamster footpad and the check pouch, an area deprived of lymphatic vessels. Typical epithelioid granulomas developed in both sites. Whereas in the footpad the size of granulomas increased and the volume of the lesion persisted, in the pouch the lesion decreased in volume. The inoculation of BCG into the footpad of animal with granulomas in the pouch, reactivated the pouch lesions. T lymphocytes were detected by an immunocytochemical technique at the edge of these lesions. Inoculation of the bacteria into the pouch induces suppressive mechanisms which hold down the volume of the lesions induced in the footpad. The cutaneous purified protein derivative (PPD) test, positive in animals inoculated in the footpad, was always negative in animals with granulomas in the pouch. The number of bacteria per microscopic field in pouch granulomas increased from 10 to 1,000 after PPD injection. Evidence that PPD has a direct effect on pouch granuloma cells is given.

Animals↗
PubMed1993

Difficulties in endoscopic removal of Teflon granulomas of the vocal fold.

The difficulties in treating granulomas resulting from Teflon injection into the vocal fold are underreported in the literature. We have reviewed our experience with nine patients undergoing 27 procedures for Teflon granuloma. Two patients required tracheotomy before undergoing endoscopic granuloma removal because of airway compromise, and a third required urgent tracheotomy following endoscopy. One of the patients requiring elective tracheotomy had a granuloma that extended across the midline to the contralateral arytenoid, causing its fixation. Arytenoidectomy was required for decannulation in this patient. In all but one patient the granuloma nearly completely replaced the thyroarytenoid muscle. This extensive involvement often precludes the adequate excision of the granuloma in a single procedure; however, the microflap technique allows mucosal preservation to facilitate future procedures. In some cases the granuloma destroys large amounts of mucosa, and a microflap cannot be elevated and saved. The difficulties of excision are related to the near-total replacement of the thyroarytenoid muscle by granuloma. This paper will help the otolaryngologist--head and neck surgeon understand this destructive process and the resulting difficulties in surgical rehabilitation.

Adult↗
PubMed1991

T and B lymphocyte subsets in spermatic granulomas in five rams.

Epididymal spermatic granulomas from five adult (greater than 4 years old) rams from a commercial flock were evaluated by quantitative histologic methods. Sections were stained for isotype specific immunoglobulin (Ig)-containing cells or specific lymphocyte subsets, as indicated by plasma membrane staining with monoclonal antibodies (MoAb). For the purpose of analysis, individual spermatic granulomas were allocated to one of three groups (early, resolving, or intermediate) on the basis of histologic examination. Ig-containing cells were most prevalent in early spermatic granulomas, and IgG-containing cells predominated in all spermatic granulomas regardless of their presumed age. IgM immunoglobulin-containing cells were the next in prevalence, and IgA-containing cells were infrequent. Assessment of lymphocyte subsets confirmed that lymphocytes present were of both T- and B-cell lineage and were well represented in all spermatic granulomas. CD4+ (MHC Class II-restricted "helper") T-cells were more prevalent in early spermatic granulomas than in intermediate or resolving types, while CD8+ (MHC Class I-restricted, "cytotoxic/suppressor") T-cells were more prevalent in spermatic granulomas of the intermediate type. These results suggest that in addition to an essentially foreign body reaction to extravasated spermatozoa, both local production of antibody and accumulation of a variety of B- and T-lymphocytes are present in ovine spermatic granulomas.

Animals↗
PubMed2000

Granuloma maturation in the rat is advanced by the oral administration of Eucommia ulmoides OLIVER leaf.

We have reported that collagen metabolism was improved by the administration of Eucommia ulmoides OLIVER leaf. In this paper, we examine the granuloma maturation and deposition of collagen in the granuloma of rats due to the oral administration of this leaf. After 3 weeks of the oral administration, granuloma formation was induced by the formalin soaked filter paper-pellet method. A week later, the developing granuloma was dissected. Granuloma formation was significantly increased due to ingestion of the dried leaf at a dose of 1.8 g/kg of body weight/d. The collagen content in the granuloma was also significantly increased. In the case of the collagen profile, the pepsin-solubilized collagen content and its relative percentage to the total collagen were significantly higher than in the control. Histochemical examination showed that the granuloma tissues were well developed, and displayed many newly synthesized capillary vessels and a greater quantity of fibroblasts and monocytes in the 1.8 g leaf group. High density lipoprotein (HDL)-cholesterol and triglyceride content in the blood plasma were significantly higher than in the control. These results show that granuloma maturation was accelerated and the energy was supplied from fatty acid metabolism. The administration of Eucommia ulmoides OLIVER leaf may be effective at speeding up the wound healing process.

Administration, Oral↗
PubMed1987

Insulin resistance of adjuvant-induced granuloma pouch formation in genetically diabetic KK-CAy mice.

The characteristics of adjuvant-induced pouch granuloma in genetically diabetic KK-CAy mice with hyperinsulinemia were investigated. Both the dose-response relationship and the time-course experiments showed that the wet weight of pouch granuloma in diabetic KK-CAy mice was lower than in ddY normal mice. Insulin treatment enhanced granuloma formation in KK-CAy mice, and it restored the suppressed DNA content in the granuloma tissue to the level in ddY mice. Although the DNA content was dose-dependently increased by insulin, the ratio of DNA content to granuloma weight was constant. In severely diabetic mice, the granuloma weight was not different from that in normoglycemic mice, despite significantly higher blood insulin levels and greater body weight. Insulin stimulated granuloma formation in severely diabetic KK-CAy mice only when higher doses (1 mg/kg) were given. This evidence suggests that suppression of granuloma formation in diabetic KK-CAy mice is due to insulin resistance and that restoration requires pharmacological doses of insulin.

Animals↗
PubMed1987

Insulin-induced granuloma tissue formation and angiogenesis in alloxan-treated diabetic mice.

Pouch granuloma formation induced by Freund's complete adjuvant containing 0.1% croton oil was studied in both normal and alloxan-induced diabetic mice, and was found to be significantly suppressed in the diabetic group. Insulin repeatedly injected into the pouch facilitated granuloma formation dose-dependently, especially in the diabetic mice. The topical insulin treatment did not affect blood glucose levels. The suppression of granuloma formation by diabetes and its reverse by insulin treatment were verified by histological findings in the granuloma pouch wall. Characteristic changes in neovascularization occurred in the pouch wall. The hydroxyproline content in the granuloma tissue in diabetic mice was not significantly enhanced by the insulin treatment. This indicates that differences in collagen production in normal and diabetic mice were not the critical factor affecting granuloma formation. It was concluded that the decreased granuloma formation in the diabetic state was due to the lack of insulin as a growth factor, and that angiogenesis induced by insulin preceding collagen fiber formation may play an essential role in granuloma formation.

Animals↗
PubMedDate not supplied

Significance of schistosomal granuloma modulation.

Hepatic Schistosoma mansoni periovular granulomas undergo changes in size, cellular composition and appearance with time. This phenomenon, known as "immunological modulation", has been thought to reflect host immunological status. However, as modulation has not been observed outside the liver, participation of local factors, hitherto little considered, seems crucial. Components of the extracellular matrix of periovular granulomas of the mouse were particularly studied in three different organs (liver, lung and intestine) and during three periods of infection time (acute, intermediate and chronic) by means of histological, biochemical and immunofluorescence techniques, while quantitative data were evaluated by computerized morphometry, in order to investigate participation of local factors in granuloma modulation. Results confirmed modulation as a exclusively hepatic phenomenon, since pulmonary and intestinal granulomas, formed around mature eggs, did not change size and appearance with time. The matricial components which were investigated (Type I, III and IV collagens, fibronectin, laminin, proteoglycans and elastin) were found in all granulomas and in all organs examined. However, their presence was much more prominent in the liver. Elastin was only found in hepatic granulomas of chronic infection. The large amount of extracellular matrix components found in hepatic granulomas was the main change responsible for the morphological aspects of modulation. Therefore, the peculiar environment of the liver ultimately determines the changes identified in schistosomal granuloma as "modulation".

Animals↗
PubMed2006

Proinflammatory cytokines in granulomas associated with murine cysticercosis are not the cause of seizures.

Neurocysticercosis is a parasitic infection of the human central nervous system caused by the cestode Taenia solium. The most common clinical manifestations of neurocysticercosis are seizures. Taenia crassiceps cysticercosis in mice has been used as an experimental model for T. solium cysticercosis. Granulomas surrounding murine cysticerci have striking immunopathological resemblance to human neurocysticercosis; early stage granulomas were able to induce seizures in a rodent model. To assess the role of proinflammatory cytokines in early stage granulomas, we isolated RNA from murine cysticercal granulomas and checked for cytokine expression by reverse transcriptase-polymerase chain reaction (RT-PCR) and/or ribonuclease (RNase) protection assays. Cytokine expression was compared with histological stages. Interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist, and tumor necrosis factor (TNF-alpha) were the major cytokines detected in all granulomas. Signals for IL-12, IL-18, and IL-6 RNA were not consistently detected and, when detected, were barely demonstrable. Expression of migration inhibitory factor (MIF), IL-6, IL-1alpha, TNF-alpha, and IL-18 was not significantly different between early and late-stage granulomas. Expression of IL-1beta, IL-1 receptor antagonist, and IL-12 p40 were higher in late, compared with early, stages. Thus, we demonstrated a broad range of cytokines in these granulomas. However, we did not document preferential expression of any proinflammatory cytokines in early stage granulomas. Thus, proinflammatory cytokines are not responsible for the seizures in the rodent model of neurocysticercosis.

Animals↗
PubMed2002

Pathogenetic roles of angiogenic factors in pyogenic granulomas in pregnancy are modulated by female sex hormones.

BACKGROUND: An abundance of microvessels is the major phenotype of pyogenic granuloma, which has been considered a hormone-related lesion based on clinical observations. Although angiogenic factors and inflammatory cytokines have been implied to play roles in the pathogenesis of pyogenic granuloma, their links to female steroid hormones still remain to be elucidated. Since apoptosis is important in limiting inflammation, we also investigated whether steroid hormones could protect granuloma cells from apoptosis and, therefore, lead to overreactive inflammatory response. METHODS: We employed immunoassays in a series of experiments, including human pyogenic granuloma in pregnancy, mouse air pouch granuloma and U937 (monoblastoid) cells in culture to clarify the relationship among vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and female steroid hormones in granuloma formation. The apoptotic rates were analyzed in vivo and in vitro by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) and flow cytometry, respectively. RESULTS: Both in human and animal studies, the immunoassays (enzyme-linked immunoabsorbent assay [ELISA] and immunohistochemistry) detected significantly more VEGF and bFGF and less TNF-alpha in hormones than the control group, while TUNEL assay revealed less apoptotic cells in groups with pregnancy levels of hormones. In vitro, progesterone enhanced the expression of VEGF in LPS-treated U937 cells. Both estrogen and progesterone inhibited the apoptosis of U937 cells triggered by exogenous TNF-a CONCLUSIONS: Female steroid hormones may have dual effects on the pathogenesis of pyogenic granuloma in pregnancy. The hormones not only enhance the expression of angiogenic factors in inflamed tissue, but also decrease apoptosis of granuloma cells to extend angiogenic effect.

Adult↗
PubMed2006

Characterization of the Histoplasma capsulatum-induced granuloma.

Rising rates of Histoplasma capsulatum infection are an emerging problem among the rapidly growing population of immune-compromised individuals. Although there is a growing understanding of systemic immunity against Histoplasma, little is known about the local granulomatous response, which is an important component in the control of infection. The focus of this article is the characterization of Histoplasma-induced granulomas. Five days after i.p. infection, infected macrophage appear in the liver and lung; however, no granulomas are apparent. Two days later, well-formed sarcoid granulomas are abundant in the lung and liver of infected mice, which contain all visible Histoplasma. Granulomas are dominated by macrophage and lymphocytes. Most of the Histoplasma and most of the apoptotic cells are found in the center of the lesions. We isolated liver granulomas at multiple time points after infection and analyzed the cellular composition, TCR gene usage, and cytokine production of granuloma-infiltrating cells. The lesions contain both CD4+ and CD8+ T cell subsets, and T cells are the primary source of IFN-gamma and IL-17. The main source of local TNF-alpha is macrophage. Chemokines are produced by both infiltrating macrophage and lymphocytes. Dendritic cells are present in granulomas; however, T cell expansion seems to occur systemically because TCR usage is very heterogeneous even at the level of individual lesions. This study is the first direct examination of host cellular responses in the Histoplasma-induced granuloma representing the specific interface between host and pathogen. Our studies will allow further analysis of key elements of host Histoplasma interactions at the site of chronic infection.

Animals↗