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Biomedical subjects

A Cipriani

Publications and source records attributed to A Cipriani.

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

Susceptibility to lysis of pulmonary alveolar macrophages by human lymphokine-activated killer cells.

In this study we addressed the question of whether lymphokine-activated killer (LAK) cells, besides killing neoplastic cells, may exert a certain degree of lysis on the normal counterpart; in particular we took into consideration the toxicity against pulmonary alveolar macrophages (PAM). We demonstrated that human LAK cells generated in vitro following incubation of peripheral blood mononuclear cells with recombinant interleukin 2 for 4 days were able to lyse normal PAM in a 4-h 51Cr release assay. Similarly, PAM recovered from patients suffering from nonneoplastic interstitial lung disorders, i.e., sarcoidosis and hypersensitivity pneumonitis, were shown to be susceptible to the cytotoxic function provided by LAK cells. Both autologous and allogeneic PAM were lysed by LAK cells, thus suggesting that the phenomenon we observed does not require a major histocompatibility complex restriction. Preincubation of PAM under study with gamma-interferon did not affect their susceptibility to the lysis mediated by LAK cells. Furthermore, cold target inhibition assay demonstrated that normal PAM could efficiently compete with both NK-sensitive and NK-resistant target lines for the binding sites on LAK cells, thus indicating that the putative receptor(s), or at least the mechanism of target recognition, is shared by PAM and these different target cell lines. The evidence herein provided that LAK cells are cytotoxic to normal, nontransformed PAM points out that the pathogenetic mechanisms involving this self-addressed lytic activity could account for some adverse reactions related to LAK/interleukin 2 immunotherapy.

Cell Line↗
PubMed1990

Immunopathology of ocular sarcoidosis.

Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. To elucidate the immunopathogenesis of ophthalmic lesions, cell infiltrates in biopsies from conjunctiva and other tissues involved (lungs, lymph nodes, skin) were studied in 26 patients with active sarcoidosis in order to define the surface phenotype and the distribution of cells in granulomatous lesions. Biopsy specimens were also stained for detection of immunoglobulins, complement and fibrinogen deposits. The data demonstrate a lymphocytes/macrophages interaction in the central core of granulomatous areas as the crucial event that initiates the maintains the state of inflammation: at all sites of disease activity is present a compartmentalization of T-cells expressing a helper-related phenotype which account for the great majority of infiltrating cells both in the early lesions (aggregate of macrophages surrounded by lymphocytic infiltrate) and in well-organized sarcoid granulomata. The presence of plasma cells and immunoglobulin deposits may represent an epiphenomenon in line with the helper infiltration, suggesting a local hyper-reactivity of the B-cells immune system. This study suggests some immunopathogenetic mechanisms leading to the formation and growth of conjunctival sarcoid granulomata.

Adolescent↗
PubMed1989

Bronchial carcinoids: a review of 60 patients.

Sixty patients with a bronchial carcinoid underwent surgical treatment. Preoperative fiberoptic bronchoscopy revealed a characteristic pink, smooth, bleeding tumor in 71.4% of the patients with a typical carcinoid and 16.7% of those with an atypical carcinoid (p less than 0.05). Eight pneumonectomies, seven bilobectomies, 34 lobectomies, three lobectomies with bronchoplasty, six bronchotomies with bronchoplasty, and two segmental resections were performed. All patients entered follow-up, and 47 were followed for more than 5 years. Ten-year survival was 89.6% for patients with a typical carcinoid and 60% for those with an atypical carcinoid. Ten-year survival was 88.1% for patients with carcinoids without lymph node involvement. All patients with lymph node involvement died within 5 years. Overall, 5 of the 8 patients having pneumonectomy died of acute cardiorespiratory failure. We conclude that a limited surgical resection with or without bronchoplasty and systematic lymphadenectomy is the procedure of choice in patients with typical carcinoids. On the other hand, atypical carcinoids are comparable to well-differentiated malignancies of the lung. Whenever possible, pneumonectomy should be avoided in favor of bronchial sleeve resection.

Adolescent↗
PubMed1989

Pulmonary alveolar macrophages from patients with active sarcoidosis express type IV collagenolytic proteinase. An enzymatic mechanism for influx of mononuclear phagocytes at sites of disease activity.

Alveolar macrophages (AMs) recovered from the bronchoalveolar lavage (BAL) of 44 patients with sarcoidosis were evaluated for their ability to release type IV collagenolytic metalloproteinase (IV-Case). This enzyme, which is produced by peripheral blood monocytes (PBMs) but not by tissue macrophages, degrades type IV collagen, the major structural component of vessel wall basement membranes, and helps to promote the migration of PBMs from the blood compartment to peripheral tissues. Our results demonstrated that AMs from patients with active sarcoidosis released significantly increased levels of IV-Case with respect to patients with inactive disease and control subjects. After in vitro culture, sarcoid AMs secreted IV-Case during the first 24 h of collection; after that time, AMs progressively lost their ability to release IV-Case. Exposition of both sarcoid and normal AMs to recombinant IL 2 or gamma IFN did not influence their property to release IV-Case. The immunoblot analysis of IV-Case demonstrated complete identity between IV-Case released by AMs and the degradative enzyme obtained from PBMs. The increased property to release IV-Case was significantly related to the increase of the absolute number of AMs and, in particular, of AMs bearing two determinants that are usually expressed by most PBMs (CD11b and CD14). Selective depletion of CD11b+/CD14+ AMs from the entire macrophagic population was associated with the recovery of the IV-Case activity to normal values. A positive correlation was also found between the increase in the absolute number of lung T cells and the enhanced CD4/CD8 pulmonary ratio. A 6-mo follow-up study indicated a significant association between the positivity for the 67Gallium scan and the increased property of AMs to release IV-Case. Our data are consistent with the hypothesis that a IV-Case mediated influx of peripheral monocytes takes place in the lung of sarcoid patients. Furthermore, the correlation found between the IV-Case release and disease activity suggests that this assay could represent a useful tool in sarcoidosis disease staging.

Adult↗
PubMed1989

Generation of superoxide anion by alveolar macrophages in sarcoidosis: evidence for the activation of the oxygen metabolism in patients with high-intensity alveolitis.

We studied superoxide anion (O2) generation by alveolar macrophages (AM) isolated from bronchoalveolar lavages (BAL) of patients with sarcoidosis, and assayed immediately after the isolation or after maintenance in culture for 2 days. In assays of cells freshly isolated from BAL, AM of patients with active sarcoidosis with a high-intensity lymphocytic alveolitis produced more O2- in response to phorbol myristate acetate than AM of patients with inactive sarcoidosis. Also, after 2 days of cultivation sarcoid AM were heterogeneous in their capability to metabolize oxygen, although both AM of active and inactive sarcoid patients produced higher amounts of O2- than AM of healthy subjects. In vitro treatment with recombinant interferon-gamma (rIFN-gamma) caused an enhancement of the capability of AM of inactive sarcoid patients to produce O2- in response to PMA. AM of patients with active sarcoidosis did not respond to rIFN-gamma when they already produced O2- vigorously. However, they became sensitive to the activating effect of rIFN-gamma after the down-modulation of their capability to produce O2-, that occurred upon prolonged cultivation. Monocytes isolated from blood of sarcoid patients and assayed immediately or after different times of cultivation did not produce more O2- than control monocytes and monocyte-derived macrophages, thus indicating that the activation of AM in sarcoidosis is likely a local phenomenon. These studies strengthen the notion that T lymphocyte-macrophage interaction is a critical event in the pathogenesis of sarcoidosis and establish that the enhanced capability to metabolize oxygen to highly reactive intermediates by AM is one of the consequence of this interaction.

Adult↗
PubMed1988

Longitudinal study of alveolitis in hypersensitivity pneumonitis patients: an immunologic evaluation.

Cells recovered from bronchoalveolar lavage were studied, both from a phenotypic and functional point of view, in 18 patients with hypersensitivity pneumonitis (HP) during a prolonged follow-up. A series of monoclonal antibodies against different lymphocyte subpopulations, including T cells, T cell subsets, and natural killer (NK) cells have been used. In some cases, an immunohistologic analysis of lung tissue sections has also been performed. The NK activity has been evaluated with regard to the in vitro function. At the time of the first evaluation, a high number of CD8+ cells with an imbalance of CD4/CD8 ratio had been demonstrated in patients with HP. Consecutive bronchoalveolar lavage evaluations demonstrated a persistent increase of CD8+ cells and a reversal of CD4/CD8 ratio in patients who continued to be regularly exposed to etiologic antigens at work (W+). In the same cases, a persistent increase of NK cells was demonstrated. Cytotoxic cells demonstrated a persistently enhanced in vitro lytic function during the follow-up, even though there appeared to be a trend toward the normal range. Patients who continued to live in agricultural environments but were not further exposed to specific antigens at work (W-) exhibited a recovery of CD4+ cells, a decrease in CD8+ cells, and an increase of CD4/CD8 ratio to the normal range 6 months after the first observation. Immunohistologic analysis, performed at the time of the first evaluation, demonstrated a diffuse infiltration of lung parenchyma by CD8+ cells, both in W+ and W- patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1988

Different types of cytotoxic lymphocytes recovered from the lungs of patients with hypersensitivity pneumonitis.

To better characterize the cytotoxic lymphocytes present in the lung of patients with hypersensitivity pneumonitis (HP), we studied cells recovered from bronchoalveolar lavage (BAL) of 5 subjects with farmer's lung disease. Specifically, this cytotoxic activity was evaluated: (1) in resting conditions and after boosting with interleukin-2 (IL-2) against NK-sensitive, NK-insensitive target cell lines, and against specific antigen-sensitized (Micropolyspora faenl) autologous monocytes; (2) after removal of NK-related populations; (3) in blocking experiments with CD3 and CD2 monoclonal antibodies. It has been demonstrated that lung lymphocytes from patients with HP in resting conditions are able to lyse both NK-susceptible and NK-resistant targets and that IL-2 is able to induce BAL cells to generate lymphokine-activated killer (LAK) cell activity. Neither resting nor activated HP lung lymphocytes were capable of specific lysis of autologous monocytes previously sensitized with specific antigen. Removal of HNK-1+ or CD16+ cells reduces, but does not completely eliminate the cytotoxic function, whereas blocking with anti-CD3 monoclonal antibody almost completely abolishes the cytotoxicity. All these data taken together suggest that different types of cytotoxic cells are recovered from the BAL of patients with HP, i.e., NK cells and non-MHC-restricted cytotoxic lymphocytes, including LAK cells.

Adult↗
PubMed1988

Immunohistochemical analysis of sarcoid granulomas. Evaluation of Ki67+ and interleukin-1+ cells.

Proliferating cells have been immunophenotypically characterized in lymph node and bronchoalveolar lavage (BAL) samples obtained from patients with active and inactive sarcoidosis with the cell-cycle-related antigen Ki67. Ki67 monoclonal antibody was used by combined immunohistochemical methods together with antibodies recognizing macrophage- and T-cell-subset-related antigens using avidin-biotin peroxidase (ABC) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) systems. Many proliferating Ki67+ cells were found in affected mediastinal lymph nodes. These cells were mainly located around granulomas and exhibited phenotypical markers of helper/inducer T cells (CD3+, CD4+). Ki67+ macrophages could not be detected in the same lesions with this technique. A different picture was found in BAL preparations where proportions of both T lymphocytes and macrophages were Ki67+. The presence of replicating lymphocytes could be correlated to disease activity, whereas the proportions of Ki67+ macrophages did not show significant differences between active and inactive disease. Interleukin-1 (IL-1) expression was investigated in the same samples with a specific antiserum. Epithelioid macrophages in granulomas and BAL macrophages in all cases exhibited cytoplasmic staining revealing an activated status. Interestingly, giant cells in granulomas were mainly devoid of IL-1 immunoreactivity. These studies support the concept that activated cells at different sites of ongoing inflammation play a central role in the mechanisms accounting for granuloma formation.

Adult↗
PubMed1987

Pulmonary alveolar macrophages in patients with sarcoidosis and hypersensitivity pneumonitis: characterization by monoclonal antibodies.

Using a panel of monoclonal antibodies (MoAbs), the frequency of cells bearing Class I and Class II major histocompatibility complex (MHC) determinants, transferrin receptor (TR) sites, and interleukin-2 receptors (IL-2R) has been evaluated on pulmonary alveolar macrophages (PAM) recovered from the bronchoalveolar lavage (BAL) fluid of 21 patients with pulmonary sarcoidosis (including 11 cases with active sarcoidosis and 10 cases with inactive disease), 8 patients with hypersensitivity pneumonitis (HP), and 6 normal non-smoking volunteers. When the frequency of Class II DR-positive cells was considered, 64.3% of control PAM expressed HLA-DR products. No statistically significant differences were observed between controls and sarcoid patients, while HP patients showed an enhanced proportion of DR+ PAM with respect to normal PAM (P less than 0.05). On the contrary, the frequency of PAM expressing HLA-DQ molecules was higher in both active sarcoidosis and HP patients with respect to patients with inactive sarcoidosis and normal subjects (P less than 0.001). A statistically significant increase in Class I antigen-positive PAM has been demonstrated in HP patients as compared to controls (P less than 0.05). Active sarcoid patients showed a higher number of PAM-bearing TR sites than controls and other groups of patients considered (P less than 0.001). An increase in the percentage of IL-2R-positive PAM has been demonstrated in active sarcoidosis (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1987

High serum levels of soluble interleukin-2 receptors in sarcoidosis.

We provide evidence that high levels of soluble interleukin-2 receptor (sIL-2R) are present in the serum of patients with sarcoidosis. Because sIL-2R is capable of binding to its ligand (IL-2), the increased serum levels of this molecule could induce a starvation of IL-2. This mechanism could help to explain a number of immunological abnormalities extensively reported in these patients and generally attributed to not yet identified serum inhibitory factors.

Adult↗
PubMed1986

Lung T cells in hypersensitivity pneumonitis: phenotypic and functional analyses.

Cells recovered from bronchoalveolar lavage (BAL) and tissue sections from transbronchial lung biopsies were studied in 16 patients with symptomatic hypersensitivity pneumonitis (HP) and in six subjects with a similar history of exposure but without features of disease by using a series of monoclonal antibodies (MoAb) detecting different lymphocyte subpopulations, including T and T subsets, B lymphocytes, and natural killer (NK) cells. Their functional activities in cytotoxic and suppressor assays and the microenvironment in the lung by using immunohistological techniques were also evaluated. It has been demonstrated that the majority of cells recovered from BAL of HP patients are represented by T8 lymphocytes, with a relevant imbalance of the T4/T8 ratio (p less than 0.001). HNK-1+ cells were markedly increased (p less than 0.001), whereas the frequency of cells bearing other NK-related markers (NK-15, VEP 13, Ab8.28, T10, M1, and Fc gamma R) were not significantly increased with respect to controls. Immunohistological study confirmed that the majority of cells infiltrating lung parenchyma are T8+ lymphocytes. The number of HNK-1+ cells detected on lung biopsies was very low in all cases, even in patients with the highest values on BAL suspensions. The evidence of cells bearing the proliferation-associated markers (Tac and T9 antigens) seems to support the hypothesis of a local proliferation in the lung. In terms of phenotypic analysis, the results observed in the group of asymptomatic individuals are qualitatively superimposable on those observed in the HP group, but the magnitude of the phenomenon is less prominent and therefore the data are not as statistically significant as that produced by the comparison between HP patients and the same controls. Functional analysis of BAL T cells from both HP patients and asymptomatic individuals showed suppressor activity in vitro, as determined by the ability to influence a pokeweed mitogen (PWM)-driven B cell differentiation assay. BAL cells from HP patients were also able to display a definite cytotoxic function in vitro, whereas BAL lymphocytes from asymptomatic subjects did not. Taken together, these data demonstrated that cells responsible for the alveolitis in patients with HP are characterized by the expansion of T cells with the phenotype and functions of both suppressor and/or cytotoxic lymphocytes. This expansion is likely to be related to a local immunologic response to the antigenic stimulus and may provide new insights into the pathogenetic mechanisms of this disease, its pathological pattern, and its management.

Adult↗
PubMed1986

Activated T cells with immunoregulatory functions at different sites of involvement in sarcoidosis. Phenotypic and functional evaluations.

Cells from recovered BAL fluid and from infiltrates in different involved tissues (lungs, lymph nodes, conjunctiva, liver, spleen, and skin) were studied in 22 patients with active sarcoidosis in order to define the surface phenotype, functional in vitro properties, and topographic distribution of the cells in granulomatous lesions. Our data demonstrated a compartmentalization of activated T cells with immunoregulatory functions from the blood to all sites of disease activity. In fact, these cells were found to express the T4+ Leu 8- 5/9+ T17- phenotype, which belongs to cells with helper activity, and that provide heightened responses in functional assays of helper activity, IL-2 release, and the ability to respond in AMLR's. Both a cellular redistribution and a local in vitro replication account for this tissue compartmentalization in sarcoidosis. The microanatomic location of activated T cells, as defined by immunohistological evaluation, showed that the state of activation in these T cells may be a consequence of an intimate contact between helper cells and macrophages within the sarcoidosis granulomas.

Adult↗
PubMed1985

Phenotypical and functional analysis of natural killer cells in sarcoidosis.

The frequency of cells reactive with natural killer (NK)-related monoclonal antibodies (MoAbs) HNK-1, NKP-15, B73.1, VEP-13, Ab8.28 has been evaluated in the peripheral blood and bronchoalveolar lavage (BAL) fluid of 39 patients with pulmonary sarcoidosis (including 19 cases with active sarcoidosis and 20 cases with inactive disease). This phenotypic analysis was carried out together with the NK in vitro functional evaluation of cell populations from peripheral blood and BAL fluid. In addition, inhibition studies were performed in order to evaluate the ability of alveolar macrophages (M phi) to modulate NK activity. Data from peripheral blood showed an increased number of mononuclear cells bearing HNK-1, NKP-15, Ab8.28, VEP-13, and B73.1 determinants in patients with active sarcoidosis with respect to patients with inactive disease and controls. The majority of HNK-1-positive cells lacked both Leu2 and Leu3 antigens when investigated in a double marker system. A parallel increase in the in vitro cytotoxicity assay has been demonstrated. On the other hand, only a few mononuclear cells recovered from BAL fluid displayed a surface pattern of NK cells. This small population of HNK-1-positive cells expresses the HNK-1/Leu3 phenotype and does not exhibit NK activity. The alveolar M phi from sarcoid patients, as well as alveolar M phi from controls, have the property of inhibiting the NK activity of autologous peripheral blood lymphocytes. The lack of lung NK function in patients with active sarcoidosis may be related to the presence of immature forms of NK cells and/or to the release of soluble factors by alveolar macrophages.

Adult↗
PubMed1985

Bronchoalveolar lavage and lung histology. Comparative analysis of inflammatory and immunocompetent cells in patients with sarcoidosis and hypersensitivity pneumonitis.

To determine whether bronchoalveolar lavage reflects the histologic aspects of the lung histology in patients with sarcoidosis and hypersensitivity pneumonitis, cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 33 patients. The evaluation of cellular types and their topographic distribution in situ was determined by using monoclonal antibodies in combination with immunohistochemical techniques. Cell counts in bronchoalveolar lavage and lung biopsies were significantly correlated both in sarcoidosis and hypersensitivity pneumonitis. In fact, the relative proportions of inflammatory and immunocompetent cells recovered from lavage fluid accurately overlapped those observed in lung tissue sections. However, in patients with more pronounced alveolitis, the frequency of macrophages in tissue sections was higher than that observed in the bronchoalveolar lavage, and the degree of lymphocytes in the lavage was higher than that observed in the corresponding biopsy. Specifically, in these patients the lavage underestimated the amount of macrophages in the lung biopsies and overestimated the number of lymphocytes that were present in the lung parenchyma. This was more evident in patients with hypersensitivity pneumonitis, where the intensity of alveolitis was higher than in sarcoidosis. Our data support the idea that, at least in patients with sarcoidosis and hypersensitivity pneumonitis, bronchoalveolar lavage correctly samples the alveolitis. Discrepancies in patients with very high intensity alveolitis could be due to a more pronounced recirculation of lymphocytes from the parenchyma to the alveolar spaces.

Adolescent↗
PubMed1985

Asymptomatic ocular sarcoidosis.

Sarcoidosis, as multisystem disease, may affect the entire visual apparatus and its adnexa: the eye hence is an optimal observation point to confirm diagnosis and assess disease activity. However, the eyes are affected only in one-fourth of cases, and the majority of the lesions are asymptomatic, requiring appropriate examination techniques to be detected. In this paper we reviewed the ophthalmic changes found in a group of 163 Italian patients affected with sarcoidosis, comparing the data collected with those published in the literature. Conjunctival granulomata, chorio-retinal lesions and lacrimal gland involvement were the more common ocular manifestations of the sarcoidosis detected; these were asymptomatic in two patients out of three. Ocular changes in sarcoidosis are more common than generally appreciated even in white patients, but their detection requires meticulous eye examination, the use of 67 Gallium scans of the head, fluorangiography, and the yield of biopsies from available eye tissues.

Adult↗