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PubMed1996

Substance P receptor antagonist inhibits murine IgM expression in developing schistosome granulomas by blocking the terminal differentiation of intragranuloma B cells.

Schistosome granulomas make substance P (SP). CP96,345 is a nonpeptide SP receptor antagonist active in vivo. Granulomas that form in the presence of SP receptor blockade produce little IgM as compared to normal lesions. The objective of this study was to determine how CP96,345 modulates granuloma IgM production. Schistosome ova were embolized to the lungs of infected mice to induce granulomas of synchronous age. Animals received CP96,345 (50 mg/kg/day) for 4 days following egg embolization. Then granulomas were isolated from tissue and dispersed into single-cell preparations. The dispersed granuloma cells were cultured in vitro to measure IgM and cytokine secretion. Also, granuloma B cells were studied using an IgM ELISPOT assay and flow cytometry. As expected, mice treated with CP96,345 formed granulomas that secreted little IgM. Granulomas from CP96,345-treated mice, as compared to buffer-treated animals, contained few IgM-secreting B lymphocytes, but had appropriate numbers of B cells expressing surface IgM. Also decreased was the capacity of the granulomas to make IFN-gamma, IL-4, IL-5 and IL-6. CP96,345 treatment did not affect splenocyte IgM or cytokine synthesis. These data suggest that CP96,345 inhibits granuloma IgM secretion by blocking intragranuloma B cell maturation at a terminal stage of B cell differentiation. Moreover, SP receptor antagonist affects a variety of cytokine circuits that could influence IgM B cell maturation in vivo.

Animals↗
PubMed2005

Conjunctival pyogenic granulomas after strabismus surgery.

PURPOSE: To measure the incidence and evaluate treatment of pyogenic granulomas after strabismus surgery. DESIGN: Retrospective observational case series. PARTICIPANTS: Four hundred seventy-nine strabismus surgical patients. METHODS: Incidence was determined by review of 472 consecutive patients who underwent strabismus surgery from January 6, 1999 to December 29, 2000. Outcomes were evaluated in 7 additional patients who underwent surgical excision of pyogenic granulomas over a 6-year period from July 5, 1995 to September 19, 2001 (exclusive of the years 1999-2000). MAIN OUTCOME MEASURE: Development and resolution of pyogenic granulomas. RESULTS: Pyogenic granulomas developed in 10 of 472 patients (2.1%). None of these patients had more than 1 pyogenic granuloma, despite having had surgery before or after the event. Treatment of pyogenic granulomas with topical corticosteroids was successful in 90% of patients. Surgical excision was successful in the group of 7 additional patients who did not respond to corticosteroids. CONCLUSIONS: Conjunctival pyogenic granulomas are a potential complication of strabismus surgery. Treatment with topical steroids is an effective initial treatment for most patients with pyogenic granulomas. Surgical excision is effective in patients who do not improve with topical medication. Patients with multiple surgeries do not seem to be at increased risk for pyogenic granulomas, and the occurrence of a pyogenic granuloma does not seem to increase the risk of developing pyogenic granulomas in future surgeries.

Child↗
PubMed2006

Immunomodulation of the hepatic egg granuloma in Schistosoma japonicum-infected pigs.

Immunomodulation of perioval granulomas is a well-known phenomenon in schistosome-infected mice, but only little is known about granuloma modulation in other animal models of human schistosomiasis. In the present study, we explored immunomodulation of egg granulomas in the liver in a pig model of schistosomiasis japonica. Granuloma size was measured and T cells, B cells and IgG(+) plasma cells in granulomas were quantified in pigs at 9, 12 and 21 weeks post infection (wpi) with Schistosoma japonicum. Granulomas were largest at 9 wpi, had decreased significantly in size at 12 wpi and remained small at 21 wpi (9 vs. 12 and 21 wpi: P < 0.05). The size of granulomas containing mature and immature eggs, respectively, did not differ significantly. The density of T (CD3epsilon(+)) cells and IgG(+) plasma cells in granulomas was the same, irrespective of granuloma size and time points. B (CD79alpha(+)) cells were rare in granulomas. The results indicate that in pigs, S. japonicum egg granulomas in the liver are immunomodulated at an early stage of infection, and that not only mature but also immature eggs induce a marked granulomatous reaction in this species.

Animals↗
PubMed1990

Interactions between adherent mononuclear cells and lymphocytes from granulomas of mice with schistosomiasis mansoni.

T-lymphocyte-adherent mononuclear cell interaction was analyzed in the vigorous and immunomodulated liver granulomas of Schistosoma mansoni-infected mice. Collagenase-dispersed granulomas contained 15% lymphocytes, 30% macrophages, 50% eosinophilis, and some neutrophils. Dispersed granuloma cells stimulated with concanavalin A or soluble worm egg antigens (SEA) did not proliferate unless plate-adherent, esterase-positive mononuclear cells were removed before culture. To analyze the granuloma adherent cell-mediated suppression, vigorous granuloma cell cultures partially depleted of adherent mononuclear cells were supplemented with indomethacin, catalase, superoxide dismutase, levamisole, and anti-murine alpha/beta interferon antiserum. In concanavalin A and SEA-stimulated cultures, only the addition of indomethacin or anti-alpha/beta interferon antiserum alleviated the adherent cell-mediated suppression of vigorous granuloma lymphocyte response. In contrast, these agents only minimally alleviated the suppressed response of SEA-stimulated, immunomodulated granuloma lymphocytes. Moreover, coculture of equal numbers of vigorous and immunomodulated granuloma cells partially depleted of adherent suppressor cells abrogated the alleviated response of vigorous granuloma lymphocytes. These findings indicate that, within the schistosome egg-induced vigorous granulomas, the adherent mononuclear cells exert regulation over lymphocyte responsiveness by alpha/beta-interferon and an indomethacin-sensitive, probably prostaglandin-mediated pathway. Within the immunomodulated granulomas, the adherent suppressor cell-mediated regulation of lymphocyte proliferation appears to play a lesser role.

Animals↗
PubMed1993

Endogenous gamma interferon is essential in granuloma formation induced by glycolipid-containing mycolic acid in mice.

The present study examined the role of endogenous gamma interferon (IFN-gamma) in the formation of granulomas in mice which had been given a single intravenous injection of glycolipid-containing mycolic acid (trehalose 2,3,6'-trimycolate) purified from cell walls of Rhodococcus aurantiacus (Gordona aurantiaca) (GaGM) in the form of liposome. The histological status of granuloma formation in the livers, spleens, and lungs of GaGM-injected mice was studied at weeks 1 through 5, and the titers of endogenous IFN-gamma in all of these organ extracts and in the sera were determined by enzyme-linked immunosorbent assay. The granulomas, composed of epithelioid cells, developed until 3 weeks postinjection, and thereafter the granulomas regressed. The production of endogenous IFN-gamma was biphasic, with an early phase detected at days 1 through 3 and a late phase detected at weeks 1 through 5. The latter peak of endogenous IFN-gamma production proceeded in parallel with granuloma formation. Both the areas of granulomas and titers of IFN-gamma in these organs were dependent on the doses of GaGM used for injection. The cells which produce endogenous IFN-gamma in the spleens appear within the granulomas. To study the role of endogenous IFN-gamma in granuloma formation, the in vivo administration of rat anti-mouse IFN-gamma monoclonal antibody was carried out. Anti-mouse IFN-gamma monoclonal antibody neutralized endogenous IFN-gamma and resulted in the suppression of the number of granulomas and the size of each granuloma. These findings suggest that biphasic production of endogenous IFN-gamma in the local lesions may be crucial to the formation and development of the granulomas.

Animals↗
PubMed2005

Epithelioid granulomas, pattern recognition receptors, and phenotypes of Crohn's disease.

INTRODUCTION: Crohn's disease is a chronic inflammatory disorder of the gut. It is assumed that a defective interaction between the bacterial flora of the gut and the innate immune system plays a key role in the pathogenesis of the disease. This may lead to specific histological lesions. The epithelioid granuloma is particularly interesting in this regard as it is also observed in several bacterial infections of the gut. AIMS AND METHODS: We hypothesised that genetic or environmental factors with a known influence on inflammation or immunity would lead to an increased prevalence of granulomas. Therefore, surgical specimens from 161 patients were evaluated for the presence of granulomas. Patients were genotyped for the three single nucleotide polymorphisms in caspase recruitment domain 15 (CARD15)/NOD2 associated with CD and for Asp299Gly in Toll-like receptor 4 (TLR4). RESULTS: The overall prevalence of granulomas was 68.9%. We did not find a significant correlation between granulomas and TLR4 or CARD15 variants. The frequency of granulomas increased with more distal disease (63% small bowel, 72% right colon, 88% left colon, 90% rectum; p=0.01). Granulomas were more frequent in younger patients (odds ratio 0.95 (95% confidence interval 0.92-0.98) p=0.007). CONCLUSION: In this study of 161 well documented CD patients, we found no significant association between CARD15 and TLR4 variants and granulomas. This finding seems to refute our initial hypothesis. However, it may be that additional factors are needed for granuloma development. Granulomas may develop only when specific bacterial components are present. Therefore, future research on granuloma pathogenesis should be orientated towards detection and identification of bacterial components in these lesions.

Adult↗
PubMed2005

Clinical significance of granuloma in Crohn's disease.

AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this study was to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course. METHODS: Fifty-six patients with newly diagnosed CD were included in the study. Jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted. RESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is more often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.

Adolescent↗
PubMed1985

Mechanisms of suppressed cell-mediated immunity and impaired antigen-induced interleukin 2 production in granuloma-bearing mice.

Pulmonary granulomas were induced in BALB/c mice immunized with methylated bovine serum albumin in complete Freund's adjuvant by the intratracheal injection of plain agarose beads or beads conjugated to specific antigen. Large hypersensitivity granulomas developed around antigen-coupled beads in immunized animals. Smaller but still prominent granulomatous reactions developed around plain beads in immunized mice. In nonimmunized animals, both plain and antigen conjugated beads produced very small granulomas. Granuloma formation in sensitized animals was associated with suppressed delayed-type hypersensitivity reactions induced by the footpad injection of specific and nonspecific antigens. Lymph node cells from sensitized granuloma-bearing mice with cutaneous anergy showed suppressed specific and nonspecific antigen-induced proliferative responses in vitro. These cells also showed suppressed interleukin 2 production in response to specific antigen. Although no soluble suppressive factor was detected in granuloma extracts, suppressor cells were found in lymph nodes of granuloma-bearing mice, which could inhibit antigen-induced production of interleukin 2 by lymph node cells from immunized mice. Antigen-specific immunoglobulin G antibody production was not suppressed in immunized granuloma-bearing mice. Previous studies from our laboratory have demonstrated migration inhibition factor and interleukin 1 activities in aqueous extracts prepared from granuloma-bearing lungs of immunized mice. These results and the findings reported here indicate that granuloma formation and the associated anergy observed in this system are primarily expressions of cell-mediated immunity; selective suppression of in vivo and in vitro expressions of cell-mediated immunity in granuloma-bearing mice may be due to impaired antigen-induced interleukin 2 production; and such impairment is caused by suppressor cells.

Animals↗
PubMed1995

Hepatic granulomas following liver transplantation. Clinicopathologic features in 42 patients.

Liver granulomas have long been known to pose diagnostic problems for pathologists; however, their prevalence and associated etiologic factors have not been studied in liver transplant patients. We reviewed 3632 liver biopsy specimens from 563 patients at two institutions and identified 42 patients with posttransplant granulomas. A possible or probable etiologic factor was identified in 30 (71%) cases. Most were epithelioid granulomas and microgranulomas located in the parenchyma associated with hepatocyte necrosis (21 cases, 50%). Portal-based granulomas were associated with recurrent primary biliary cirrhosis (5 cases, 12%), acute cellular rejection (2 cases, 4.8%), and a foreign body-type reaction (1 case, 2.4%). One case was associated with tuberculosis (2.4%), 4 cases occurred in a fatty liver (9.5%), and 8 patients had liver granulomas but no other significant abnormality. The granulomas were most frequent in the first 7 months after transplantation when the patients were biopsied more often and underwent episodes of rejection or acute hepatitis. Portal-based granulomas in this period were usually associated with acute cellular rejection. After 7 months, the frequency of granulomas as well as the number of biopsies decreased and portal-based granulomas associated with recurrent primary biliary cirrhosis were most common (5 cases, 12%). Rare, late-appearing parenchymal granulomas were also seen (3 cases) and consisted of 1 lipogranuloma and 2 cases of epithelioid granuloma. The latter were thought, in 1 patient, to be associated with parenchymal hepatocyte necrosis; the others were of unknown etiology.

Biopsy↗
PubMed1995

Two waves of gamma delta T cells expressing different V delta genes are recruited into schistosome-induced liver granulomas.

Isolated granulomas provide a unique model to study T cells in the site of inflammation. Schistosoma mansoni-infected mice develop liver granulomas in response to schistosome egg deposition and the granulomas contain gamma delta T cells that appear to be activated (Pgp-1high and L-selectin low). Analysis of kinetics and TCR gene usage of granuloma gamma delta T cells revealed a limited TCR repertoire restricted to V gamma 1.1, V delta 4, and V delta 6 genes, suggesting that the occurrence of gamma delta T cells in the granuloma is influenced by TCR V gene usage. The V delta 4+, but not the V delta 6+, gamma delta T cells expressed CD69, a marker of recent activation. To determine if there was a preferred order of accumulation of the gamma delta T cells in granulomas, s.c. sponge grafts were implanted into schistosome-infected mice, schistosome eggs were injected into the grafts, and accumulated T cells were sequentially analyzed. The earliest gamma delta T cell immigrants expressed V delta 6 and later immigrants expressed V delta 4 V genes. Additional evidence for a role of TCR specificity in the accumulation of gamma delta T cells in granulomas is their absence from schistosome granulomas in TCR transgenic mice that express only a single MHC-specific gamma delta TCR. Finally, gamma delta T cell recruitment into the granulomas did not require beta 2-microglobulin, since gamma delta T cells were present in liver granulomas of beta 2-microglobulin gene-disrupted mice. The analysis of the influx of gamma delta T cells into schistosome-induced, liver granulomas and schistosome egg-containing sponges provides a model system to investigate the role, if any, of gamma delta T cells in schistosome infections.

Animals↗
PubMed1994

Inflammatory granuloma formation is mediated by TNF-alpha-inducible intercellular adhesion molecule-1.

Recent studies have demonstrated a crucial role for TNF during inflammatory granuloma formation. In addition, TNF has been shown to up-regulate adhesion molecules that participate in cellular recruitment and lymphocyte activation. In the present study, we have examined the mechanism of TNF activation during Schistosoma mansoni egg granuloma formation and its relationship to the expression of ICAM-1. Our initial studies showed that high affinity human soluble TNFR coupled to the Fc portion of an Ig (sTNFR:Fc construct) could effectively diminish granuloma formation and lymphocyte activation in vivo. We have also assessed the increased expression of ICAM-1, its contribution to granuloma development, and its relationship with TNF during lesion formation. Increased steady state ICAM-1 mRNA expression was observed in primary egg granulomas when compared with normal lung and foreign body (Sephadex bead) granulomas, which suggests a role for ICAM-1 in Ag-induced lesion formation. Subsequent studies have demonstrated that sTNFR:Fc treatment down-regulated granuloma formation and ICAM-1 expression, thus suggesting one mechanism of TNF involvement in granuloma formation was through the induction of ICAM-1. Anti-ICAM-1 decreased the soluble egg Ag-specific T cell proliferation in vitro. In addition, passive immunization of mice with anti-ICAM-1 mAb during primary granuloma formation resulted in an attenuation of lesion development as compared with lesion development in a control Ab-treated group. The proliferative response to soluble egg Ag was also significantly reduced in ex vivo experiments that used spleen cells from the anti-ICAM-1 treated mice. These data demonstrate that both TNF and ICAM-1 participate in lymphocyte activation and granuloma formation and suggest that one mechanism of TNF in granuloma development is through TNF-induced ICAM-1 expression.

Animals↗
PubMed1995

[Logopedic rehabilitation of laryngeal granulomas].

Posterior laryngeal granuloma is an infrequent pathology of multidisciplinary interest. Actually, its real prevalence is difficult to quantify because in some cases it is asymptomatic and in other instances it may either be reabsorbed or eliminated spontaneously. It is located at the vocal apophysis of the arytenoid or, less frequently, above it or on the laryngeal side of the arytenoid. The many etiologic factors (laryngeal intubation, gastro-esophageal refluxes, blunt trauma of the larynx, vocal dysfunction), sometimes concomitant and with the possible addition of enhancing circumstances (upper aerodigestive tract inflammation, naso-gastric tube, smoking and alcohol abuse), converge to a single pathogenetic mechanism: an ulceration of the mucosa and the pericondrium, sometimes complicated by an infection, which does not heal but instead produces a typical granulation tissue with capillaries oriented radially from the center of the lesion. Post intubation granulomas, extremely rare in children, are more frequent in females. It appears that there is no correlation with duration of intubation in that granulomas, can also occur after short general anesthesia. Idiopathic or contact granulomas are more frequent in the males. They are the result of vocal laryngeal hyperfunction, habitual throat clearing or cough-like throat clearing. Gastro-esophageal reflux of gastric juice, coughing or throat clearing may injure the mucosa. A blunt trauma of the larynx may cause a granuloma if the cartilage of the vocal process is exposed. Symptoms, when present, are dysphonia, tiredness during or after voicing, bolus, laryngeal unilateral pain, sensation of something in the throat which is mobile during breathing and swallowing, traces of blood in the expectoration. Therapeutic options are surgical, medical or logopedic. Surgery, although followed by frequent recurrences, is mandatory when the granuloma causes dispnea or if a pathologic essay is needed. Medical treatment aims at solving gastroesophageal reflux and/or inflammations of the district. Logopedic rehabilitation is the most successful therapy. Since January 1992 the Authors have been adopting the rehabilitation protocol planned by the French phoniatrician Brigitte Arnoux-Sindt for post-intubation granulomas, which, moreover, is utilyzed for all type of granulomas, including those arising during the early postoperative period after cordectomy. This protocol is analytically presented and discussed. In the cases of contact granulomas, and when there is concomitant vocal dysfunction, logopedic treatment is prolonged after granuloma dissapearance with some sessions aiming at restoring correct vocal behaviour. In all the ten patients rehabilitated up to now, granulomas disappeared after a mean of 16.3 sessions held twice a week. After several months of follow-up we had no recurrences. This clinical experience, while limited in number, seems to confirm the good results already reported in French Literature.

Adolescent↗
PubMed1998

Localization and regulation of IFN-gamma production within the granulomas of murine schistosomiasis in IL-4-deficient and control mice.

Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice make little IFN-gamma and show no Th1 polarization. This could signify that these granulomas have few cells capable of IFN-gamma synthesis or that such cells are under tight control. Granulomas can make IL-10 and TGF-beta, which can regulate IFN-gamma synthesis. Using FACS analysis and ELISA, we explored the origin and regulation of IFN-gamma in schistosome granulomas from both IL-4(-/-) and IL-4(+/+) mice. FACS analysis of intracytoplasmic IFN-gamma staining showed that some granuloma Thy1.2+ T cells (CD8+ and CD4+) express IFN-gamma. Granulomas had NK1.1+ cells, but they appeared to produce little or no IFN-gamma. Purified granuloma Thy1.2+ cells made IFN-gamma in vitro, whereas isolated NK1.1+ lymphocytes secreted little even with rIL-12 stimulation. Culture of granuloma cells with blocking anti-IL-10 or anti-TGF-beta mAb or with rIL-12 substantially increased T cell IFN-gamma synthesis, particularly in the IL-4(-/-) animals. Cultured granuloma cells depleted of Thy1.2+ lymphocytes by Ab and C released no IFN-gamma. It is concluded that granuloma IFN-gamma comes from T cells, not NK cells. Also, this T cell-derived IFN-gamma is subject to IL-10 and TGF-beta regulation, which is particularly evident in IL-4(-/-) mice. Thus, the Th2 granuloma of schistosomiasis has large numbers of activated Th1 or Th0 lymphocytes that are under tight restraint.

Animals↗
PubMed1999

Activated eosinophils are the major source of Th2-associated cytokines in the schistosome granuloma.

Eosinophils are a numerically dominant cell population within the schistosome granuloma. These granuloma eosinophils can produce a variety of cytokines, including IL-2, IL-4, IL-5, and IFN-gamma. Therefore, eosinophils may play a key role in the determination of the unique cytokine microenvironment within the granuloma milieu. These studies investigated the potential role of eosinophils in the regulation of granuloma immunopathology. We have characterized spleen- and granuloma-derived eosinophils based on cellular activation and cytokine production during the development of murine schistosomiasis. Based on the criteria of hypodensity and CD69 expression, granuloma eosinophils were highly activated and very homogeneous at 7 and 11 wk postinfection. Splenic eosinophils were also activated at 7 wk postinfection, but were much more heterogeneous than their granuloma counterparts. By 11 wk postinfection, few hypodense splenic eosinophils were observed. Eosinophils represented the majority of cytokine-producing cells in the granuloma and were a dominant source of IL-4. Eosinophils also produced IL-2, IL-5, and IFN-gamma, using the criteria of mRNA in situ hybridization and intracellular cytokine staining by FACS. Granuloma eosinophil activation and cytokine production were greatest at the time of maximum granuloma formation, i.e., 10-12 wk after initial cercarial exposure. Therefore, locally activated eosinophils, not Th2 lymphocytes, produce the majority of Th2 cytokines in the granuloma milieu and may be important determinators of immunopathology in schistosomiasis.

Animals↗
PubMed2004

Different histologic patterns of cutaneous granulomas in systemic lymphoma.

BACKGROUND: Patients with Hodgkin's and non-Hodgkin's lymphomas may develop non-infectious granulomas in both involved and uninvolved organs, but rarely in the skin. Cutaneous granulomas in the setting of a systemic lymphoma are of two types. The first type is characterized by granulomatous infiltrates admixed with neoplastic cells within specific skin lesions of malignant lymphomas. The second type consists of granulomatous skin processes that are non-specific manifestations of the underlying lymphoma. OBJECTIVE: To describe the variegate histologic patterns of cutaneous granulomatous reactions of the second type in patients with systemic lymphomas. METHODS: We describe three patients with systemic lymphomas who exhibited three different histologic patterns of cutaneous granulomatous lesions. RESULTS: The first patient had non-Hodgkin's lymphoma with cutaneous tuberculoid-type granuloma mimicking tuberculoid leprosy; the second patient had Hodgkin's lymphoma with palisaded, necrobiotic granuloma of granuloma annulare-type; and the third patient had non-Hodgkin's lymphoma with sarcoid-type granuloma. No evidence of the underlying systemic lymphoma was found in the cutaneous lesions involved by the granulomatous process. CONCLUSIONS: Cutaneous granulomas may be a non-specific sign of an underlying systemic lymphoma. Their histologic patterns are variegate and include sarcoid-type granuloma, palisaded and necrobiotic granuloma of granuloma annulare-type, and tuberculoid granuloma. In patients who present with non-infectious, granulomatous skin reactions in the absence of another sound explanation, the possibility of a systemic lymphoma should be considered.

Adult↗
PubMed1980

Hepatic granulomas induced by glucan. An ultrastructural and peroxidase-cytochemical study.

Granulomas were induced in rat liver by the injection of glucan, a beta-1,30-polyglucose with an activating effect on macrophages. The livers were fixed by perfusion with glutaraldehyde and processed for cytochemical localization of peroxidase (PO) as well as for scanning and transmission electron microscopy. By light microscopy the granulomas appeared as spherical cell clusters located throughout the liver parenchyma. They exhibited strong PO activity at the periphery with weak to negative reaction at the center. Most granulomas were in direct continuity with adjacent sinusoids. Morphometry revealed that the volume of granulomas increased to about 10 per cent of the total parenchymal volume at 10 days after glucan treatment, decreasing to less than 2% at 90 days. By scanning electron microscopy most cells at the periphery of granulomas were covered with numerous blebs and ruffles, the typical surface features of activated macrophages. By transmission electron microscopy the typical granulomas consisted of mononuclear phagocytes, giant cells, and a few lymphocytes. The phagocytes, as identified by phagocytosis of glucan, exhibited three distinct PO patterns: (1) strong PO activity in the nuclear envelope and endoplasmic reticulum with no activity in cytoplasmic granules; (2) weak or absent reaction in nuclear envelope and endoplasmic reticulum with no PO-positive granules in cytoplasm; and (3) absent reaction in nuclear envelope and endoplasmic reticulum but with a few strongly stained cytoplasmic granules. The first cell type, resembling Kupffer cells, was found mainly at the granuloma periphery. The second cell type, identified ultrastructurally as epithelioid cells, and the third cell type, with PO features of monocytes, were found mainly in the center of granulomas. The multinucleated giant cells which were also present in the center of granulomas exhibited weak to negative PO reaction in nuclear envelope and endoplasmic reticulum and contained large numbers of glucan particles. These observations suggest that most cells in the center of the granulomas, including the giant cells, are derived from blood monocytes. The mononuclear phagocytes at the periphery, on the other hand, seem to be for the most part former Kupffer cells.

Animals↗
PubMed1994

Contact granulomas of the larynx.

Ten cases of intubation granulomas and eight cases of contact granulomas not related to intubation were reviewed for the purpose of clinical analysis and pathological investigation. Granulomas were located primarily at the vocal process of the arytenoid cartilage. Additionally, 58 hemilarynges obtained from 37 cadavers with intubation granulomas were evaluated grossly and histopathologically. The intubation granulomas had no side predilections. All eight contact granulomas occurred in males and had a higher incidence of recurrence (three of eight cases) despite complete removal with laser surgery. In an attempt to explain recurrences of these contact granulomas, all three cases were studied clinically and pathologically. Results indicated that they recurred in singers and vocal abusers, and presumably resulted from the continued hammering of one vocal process against the other. Analysis also demonstrated that vocal rehabilitation was essential prior to or immediately after removal of the granuloma to prevent its recurrence. Pathological evaluation of the contact granulomas revealed focal ulceration and a covering of necrotic tissue with desquamating epithelium. The propria mucosa was edematous and infiltrated by chronic inflammatory cells and neutrophils forming focal granulation tissue in a stroma containing proliferated capillaries. Pathological features around local ulcerations were typical of a secondary granuloma while underlying arytenoid cartilage was partially necrotic.

Adult↗
PubMed1985

Autoradiographic studies of cell dynamics in immunogenic granulomas transplanted into the skin of athymic nude mice.

Schistosome egg granulomas in the livers of thymus-intact (nu/+) mice are large and contain eosinophils and mast cells, while those in nude athymic (nu/nu) mice are small and devoid of eosinophils or mast cells. To investigate the cell sources and cell kinetics of hepatic granulomas of nu/+ mice isolated and grafted into the skin of nu/nu mice, biopsies taken after grafting were examined by light and electron microscopy and autoradiography after 3H-thymidine (TdR) injection of either the donor or recipient mice. At 1 week, the grafted granulomas appeared to be amorphous and were surrounded by leukocytes, and the 3H-TdR-labeled donor cells had disappeared. After 2 weeks, repopulation with macrophages began and by 3-5 weeks, the granulomas morphologically resembled hepatic lesions of nu/+ mice. Injection of recipients with 3H-TdR before grafting, showed that labeled macrophages, eosinophils, and mast cells repopulated in granulomas. No granulomas were seen when nu/nu mice were grafted with schistosome eggs alone, and organ culture of nu/+ granulomas before grafting reduced the number of repopulated granulomas. These findings indicate that nu/+ cells in grafted granulomas are replaced by nu/nu cells. Granulomatous reaction of the grafted sites in nu/nu mice is influenced by a substance in nu/+ granulomas, and cells of nunu mice locally acquire a nu/+ type response.

Animals↗