Search PubMed⌕ Search

Biomedical subjects

Carlo Agostini

Publications and source records attributed to Carlo Agostini.

At least 37 records · Page 2Linked to original sources
PubMed2005

CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic arthritis.

The accumulation of T cells in the synovial membrane is the crucial step in the pathophysiology of the inflammatory processes characterizing juvenile idiopathic arthritis (JIA). In this study, we evaluated the expression and the pathogenetic role in oligoarticular JIA of a CXC chemokine involved in the directional migration of activated T cells, i.e. IFNgamma-inducible protein 10 (CXCL10) and its receptor, CXCR3. Immunochemistry with an antihuman CXCL10 showed that synovial macrophages, epithelial cells, and endothelial cells bear the chemokine. By flow cytometry and immunochemistry, it has been shown that CXCR3 is expressed at high density by virtually all T lymphocytes isolated from synovial fluid (SF) and infiltrating the synovial membrane. Particularly strongly stained CXCR3+ T cells can be observed close to the luminal space and in the perivascular area. Furthermore, densitometric analysis has revealed that the mRNA levels for CXCR3 are significantly higher in JIA patients than in controls. T cells purified from SF exhibit a definite migratory capability in response to CXCL10. Furthermore, SF exerts significant chemotactic activity on the CXCR3+ T-cell line, and this activity is inhibited by the addition of an anti-CXCL10 neutralizing antibody. Taken together, these data suggest that CXCR3/CXCL10 interactions are involved in the pathophysiology of JIA-associated inflammatory processes, regulating both the activation of T cells and their recruitment into the inflamed synovium.

Adolescent↗
PubMed2005

Arterio-venous gradient of endothelial progenitor cells across renal artery stenosis.

A role for circulating progenitor cells have been recently demonstrated in many pathological conditions. Endothelial progenitor cells (EPCs) localize at sites of ischemia and stimulate neovasculogenesis. This small study was carried out to assess whether selective blood sampling during renal angiography could demonstrate an arterio-venous gradient of EPCs in 5 patients with renal artery stenosis. Surprisingly, we found that EPCs were more abundant in venous than in arterial blood, suggesting that the kidney subjected to chronic ischemia may become a source rather than a target of EPCs.

Endothelium, Vascular↗
PubMed2005

Modulation of immune response by the acute and chronic exposure to high altitude.

PURPOSE: The chronic exposure at high altitude (HA) represents an ideal model for evaluating the in vivo effects of hypobaric hypoxia. Taking advantage of the EV-K2-CNR Pyramid, this study was designed to evaluate whether acute and chronic hypoxia differently modulates the in vivo immune responses. METHODS: The study includes 13 healthy female moderately active volunteers participating to the Italian HA project EV-K2-CNR. Peripheral blood lymphocytes, collected at sea level and at HA in the Pyramid Laboratory of CNR, Nepal (5050 m), were immunologically characterized by flow cytometry and a series of molecular and functional analyses. RESULTS: Flow cytometric analyses showed that: a) CD3+ T lymphocytes significantly decreased during both acute and chronic exposure to HA, b) T-cell fall was totally due to CD4+ T-cell reduction, c) B lymphocytes were not influenced by the exposure to HA, and d) natural killer (NK) cells significantly increased during acute and chronic exposure. The evaluation of the Th1/Th2 pattern demonstrated a significant decrease of the expression of the Th1 cytokine interferon-gamma (IFN-gamma) by circulating T cells during acute and chronic exposure to HA. The expression by T cells of CXCR3, a chemokine receptor typically expressed by Th1/Tc1 cells, paralleled the decrease of IFN-gamma. On the contrary, the expression of IL-4 was not conditioned by the exposure to HA. Finally, functional studies showed a significant reduction of the proliferative activity in response to mitogen (PHA) both in acute and chronic HA exposure. Despite the increased number of NK cells, NK cytotoxic activity was not influenced by the HA exposure. CONCLUSIONS: Our results indicate that the in vivo exposure to HA leads to an impairment of the homeostatic regulation of Th1/Th2 immune balance that potentially could favor long-term immunological alterations and increase the risk of infections.

Adult↗
PubMed2005

NOD2/CARD15 gene polymorphisms in idiopathic pulmonary fibrosis.

BACKGROUND: Micro-organisms, behaving in a non-infectious fashion, may be among the exogenous factor(s) believed to trigger idiopathic pulmonary fibrosis (IPF). One possible strategy to identify an individual's susceptibility to such microbial triggers, which are likely to be ubiquitous, is to investigate the molecular processes involved in their recognition. NOD2/CARD15 is a specific pattern recognition receptor protein, whose genetic variants have been previously associated with susceptibility to Crohn's disease. AIM: The aim of this work was to determine the frequencies of the three major NOD2/CARD 15 gene mutations (R702W, G908R and 1007fsinC) in a series of 76 subjects affected by IPF, and to compare them with those found in three groups of controls: a group with sarcoidosis (a disorder in which an involvement of the NOD2/CARD15 gene has already been investigated and rejected in different ethnic groups; 67 subjects) and two groups of healthy subjects (218 and 208 subjects, respectively), matched for gender, age, and ethnicity. RESULTS: We found no differences in frequencies of NOD2/CARD15 gene polymorphisms among the four groups investigated. CONCLUSION: We conclude that the NOD2/CARD15 gene is not likely to be involved in susceptibility to IPF in Italians.

Aged↗
PubMed2005

New frontiers for rare pulmonary diseases.

This Issue of Sarcoidosis Vasculitis and Diffuse Lung Diseases is dedicated to a special event which was held in Milan in February 2005. The First International Conference on Rare Pulmonary Diseases and Orphan Drugs in Respiratory Medicine brought together for two days most of the leading world authorities in the field of interstitial lung diseases. Over 200 investigators from 9 different countries convened to assess current knowledge in the field of pathogenesis, diagnosis and therapy of rare lung disorders. An incredible amount of data was discussed during the meeting, testifying to the recent advances in the clinical management of these diseases.

Alveolitis, Extrinsic Allergic↗
PubMed2005

Cytokines, chemokines and other biomolecular markers in sarcoidosis.

In recent years our knowledge in terms of the network of interactions between immunocompetent cells that set the stage for the pathogenesis of sarcoidosis has continuously improved. Remarkable advances have been made in understanding general immunological and molecular aspects of the mechanisms leading to granuloma formation. In this manuscript we will review the current concepts on cellular interactions which define regulatory networks ultimately contributing to the granuloma formation at sites of disease activity in sarcoidosis. The biological effects of Th1 and Th2 cytokines in sarcoid lung will be taken into account and the importance of the local production of those chemokines and cytokines whose release has been recently demonstrated within the lung of patients with sarcoidosis will be emphasized.

Biomarkers↗
PubMed2004

Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas.

This study investigated the role of several chemokines and their receptors on malignant B lymphocytes recovered from 13 patients with chronic lymphocytic leukemia (CLL), 9 with hairy cell leukemia (HCL), 5 with mantle cell lymphoma (MCL), 5 with marginal zone B-cell lymphoma (MZL), 6 with small lymphocytic lymphoma (SLL), and 5 with follicular cell lymphoma (FCL). Flow cytometry analysis demonstrated that CXCR4 and CXCR5 were expressed on all malignant and normal B cells. Considering CC receptors, CCR1 was expressed in 70% of patients with CLL and 40% of those with HCL but was lacking in patients with MCL, MZL, SLL, and normal B cells. CCR2 showed a heterogeneous pattern of expression. CCR3 was found in almost all patients with CLL and in the majority of those with HCL, whereas it was usually lacking in patients with MZL and SLL and in healthy subjects. CCR5 was expressed in patients with HCL and MCL. Migration assays showed that different chemokines, mainly CXCL12 and CXCL13, are able to trigger migration of malignant B lymphocytes. Some of these chemokines induce calcium mobilization. These data indicate that different patterns of chemokine receptor expression identify different malignant B-cell subsets and that these receptors are functional and might play a role in malignant B-cell circulation.

Aged↗
PubMed2004

T cells in the lung of patients with hypersensitivity pneumonitis accumulate in a clonal manner.

Hypersensitivity pneumonitis (HP) is characterized by an alveolitis sustained by CD8(+) T lymphocytes showing a limited expression of the T cell receptor (TCR). We previously demonstrated that a bias in T cell selection occurs in the lower respiratory tract of patients with HP, with a compartmentalization in the lung of CD8(+) T cells bearing (TCR)-beta variable (TCRBV) #2, 3, 5, 6, 8, and 13 gene segments. We herein characterized the clonal T cell populations present in the lung and in the blood of patients with HP. Heteroduplex analyses, cloning, and sequencing T cells bearing TCR indicate oligoclonal expansions of T cells expressing homologous or identical complementary-determining region 3. Furthermore, T cell clones isolated from the two compartments expressed similar, sometimes identical, junctional regions. Removal from antigenic exposure led to the disappearance of T cell clones. Our findings indicate that expansions of T lymphocytes bearing clonal TCRBV region gene segments take place in the lung of patients with HP during exposure. The evidence that identical T cell clones are present in the lung and the blood of the same patient suggests that the immune reaction occurring at lung level gives rise to a systemic reaction.

Adult↗
PubMed2004

Overexpression of tumor necrosis factor (TNF)alpha and TNFalpha receptor I in human viral myocarditis: clinicopathologic correlations.

Proinflammatory cytokines, including tumor necrosis factor (TNF)alpha, have been recognized as important physiopathogenetic factors in the initiation and continuation of inflammatory cardiomyopathies. Experimental and preliminary human studies have demonstrated that TNFalpha plays a crucial role in enteroviral-induced myocarditis. In this study, we investigated the expression of TNFalpha and both its receptors (TNFRI and TNFRII) in both viral and nonviral myocarditis. Myocardial expression of TNFalpha was then correlated with different clinical and pathologic findings. TNFalpha expression was investigated in endomyocardial biopsies obtained from 38 patients with myocarditis and from eight control subjects by using reverse transcriptase-polymerase chain reaction (PCR) and immunohistochemistry. Viral etiology was diagnosed by PCR in 20 cases: enterovirus in seven, Epstein-Barr virus in four, hepatitis C virus in three, adenovirus in two, influenza virus in two, cytomegalovirus in one, and double infection adenovirus and enterovirus in one. Immunohistochemistry was also used to analyze both TNFalpha receptors (RI and RII). A semiquantitative analysis was employed (score 0-3) for necrosis, inflammation, fibrosis and immunohistochemical findings. TNFalpha mRNA and TNFalpha protein were significantly more present in viral myocarditis than in nonviral myocarditis (16/20 vs 3/18, P=0.001). Remarkable immunostaining was observed for both receptors, particularly TNFRI. Histological analysis revealed that myocardial necrosis (mean score 1.89 vs 1.15, P=0.01) and cellular infiltration (mean score 2.26 vs 1.78, P=0.05) were more prominent in TNFalpha-positive cases. Among TNFalpha-positive cases, the greater TNFalpha mRNAs, the more impaired was cardiac function. Our findings suggest that the expression of TNFalpha may play an important role in the pathogenesis of viral myocarditis of any etiology and may influence the severity of cardiac dysfunction. Cytokine effects are more strictly linked to overexpression of TNFRI.

Adolescent↗
PubMed2004

New aspects of hypersensitivity pneumonitis.

PURPOSE OF REVIEW: Hypersensitivity pneumonitis (HP) represents a complex pulmonary disorder of varying intensity and clinical presentation, which is characterized by a diffuse Tc1 immune response of lung parenchyma and airways in patients previously sensitized to one of more than 300 etiologic agents that may favor the HP reaction. This review describes recent data that have clarified some of the events that govern the development of the hypersensitivity reaction following exposure to the causative agents involved in this disease. RECENT FINDINGS: A number of recent data clearly demonstrate that several cytokines and chemokines, which are secreted at sites of disease activity, participate in the pulmonary inflammatory responses taking place in the lung of patients with HP. SUMMARY: The past few years have seen outstanding advances in the understanding of immunologic and molecular events involved in the pathogenesis of HP. It is possible that these data could allow the discovery of therapeutic targets in individuals chronically exposed to HP antigens and evolving towards pulmonary fibrosis.

Alveolitis, Extrinsic Allergic↗
PubMed2004

Tailoring immunosuppressive therapy in interstitial lung diseases.

An increasing number of immunosuppressive drugs have become available for clinical use over the past few years. Respiratory medicine has not been excluded from the growing enthusiasm devoted to the use of novel immunosuppressants. New agents are currently undergoing clinical trials in pulmonary disorders characterized by acute or chronic inflammation, the "optimal" immunosuppressive strategy for the cure of interstitial lung diseases in the next decade being forthcoming. An example of this fervour may be found in this issue of the Journal; data have been provided on the effectiveness in clinical use of an inhibitor of nucleotide synthesis, leflunomide, in chronic sarcoidosis. The great choice of available agents could allow us to select the best therapeutic regimen for an individual patient, however, this requires a comprehensive knowledge of the modes of action of the immunosuppressants we are planning to use. The present review provides an update of current understanding on the molecular mechanisms of some important immunosuppressants that are expected to play a role in the therapy of interstitial lung diseases.

Alkylating Agents↗
PubMed2003

Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes.

Using monoclonal antibodies (mAbs) specific for different natural killer (NK) receptors, we studied the lymphocyte population from 18 patients with NK-type lymphoproliferative disease of granular lymphocytes (LDGL). The analysis of both resting and cultured NK cell populations demonstrated that these patients are frequently characterized by NK cells displaying a homogeneous staining with given anti-killer Ig-like receptor (anti-KIR) mAb (11 of 18 patients). In most patients NK cells were characterized by the CD94/NKG2A+ phenotype, whereas only a minor fraction of the cases expressed CD94/NKG2C. In 7 of these patients we could also assess the function of the various NK receptors. Remarkably those KIR molecules that, in each patient, homogeneously marked the NK cell expansion were found to display an activating function as determined by cross-linking with specific anti-KIR mAb. The KIR genotype analysis performed in 13 of 18 cases revealed that in NK-type LDGL certain activating KIRs, as well as certain infrequent KIR genotypes, were detected with higher frequencies as compared to previously analyzed healthy donors. Moreover, most KIR genotypes included multiple genes coding for activating KIRs. The analysis of non-HLA-specific triggering receptors indicated that the natural cytotoxicity receptors (NKp46, NKp30) were expressed at significantly low levels in freshly drawn NK cells from most patients analyzed. However, in most instances the expression of NKp46 and NKp30 could be up-regulated on culture in interleukin 2. Our data indicate that in NK-LDGL the expanded subset is frequently characterized by the expression of a given activating KIR, suggesting a direct role for these molecules in the pathogenetic mechanisms of this disorder.

Antibodies, Monoclonal↗
PubMed2003

Upregulation of CXCR1 by proliferating cells in patients with lymphoproliferative disease of granular lymphocytes.

The expression and the functional activities of different chemokine receptors (CC motif: CCR1, CCR2, CCR3, CCR5, CCR6; CXC motif: CXCR1, CXCR2, CXCR3, CXCR4, CXCR5) were investigated in 12 patients with lymphoproliferative disease of granular lymphocytes (LDGL). Six patients were characterized by the proliferation of CD3+ve GL and six patients by the expansion of CD3-ve GL. The interleukin 8 (IL-8/CXCL8) receptor CXCR1 was expressed in 12/12 patients, the CXCR4 in 6/12 patients (four CD3+ve and two CD3-ve) and the CXCR3 in 3/12 patients (one CD3+ve and two CD3-ve). CXCR1 was expressed only by proliferating GL. Other CC and CXC receptors were not expressed on proliferating GL (< 2%). In functional assays, purified GL from the patients displayed significant migration in response to specific chemokines, indicating that CXCR1, CXCR3 and CXCR4 were functionally active in these patients. In addition, a significant reduction of IL-8/CXCL8-mediated cell migration was reported in the presence of anti-CXCR1 monoclonal antibody. Our results indicate that expanding cells from patients with LDGL express specific CXCR. These data may help to define functional properties of proliferating GL in patients with LDGL and contribute toward the understanding of the complex clinical features of this disease. In particular, as CXCR1 was expressed in all of the patients studied, we speculate that abnormal expression of this receptor on proliferating GL might play a role in the pathogenesis of neutropenia, which represents a common feature in LDGL patients.

Cell Division↗
PubMed2003

Chronic obstructive pulmonary disease (COPD): new insights on the events leading to pulmonary inflammation.

The presence of a heterogeneous infiltrate of macrophages, neutrophils and CD8+ Tc1 cells is a characteristic feature in the lung of patients with chronic obstructive pulmonary disease (COPD). This paper points out the contribution of different inflammatory cells and mediators to the pathogenesis and natural history of COPD. We will comment on data suggesting that CD8 cytotoxic T cells with an activated Tc1 phenotype migrate from the secondary lymphoid tissue to pulmonary tissue damaged by smoke or infective agents. On the basis of the knowledge of the pathophysiology of immunologic events, drugs that can potentially block the inflammation leading to the disability of COPD are being investigated. Long-term study in a large number of patients with COPD will be needed to verify the impact of a number of anti-inflammatory compounds in this increasingly common disease.

Benzoates↗
PubMed2002

T-lymphocytes and cytokines in sarcoidosis.

In the last few years, a number of reports have clearly shown that pulmonary T lymphocytes have evolved a number of effector mechanisms to respond to foreign antigens, ranging from direct cytotoxicity mechanisms to secretion of lymphokines, that have the ability to activate themselves or other pulmonary immunocompetent cells. Furthermore, there is also evidence that lung T cells may have a role in the immunopathogenetic mechanisms taking place in the lung of most immune-mediated diffuse lung disorders. In this paper, we will review the current concepts on the recruitment, homing, and activity of T lymphocytes in the lower respiratory tract of patients with sarcoidosis. The relevant phenotypic and functional abnormalities detected on T cells in sarcoidosis will be discussed. Furthermore, we will comment recent findings on the ability of immunomodulatory molecules, such as proinflammatory cytokines, chemokines, and other cytokines, to regulate T-cell function in immune mechanisms leading to granuloma formation and maintenance.

Apoptosis↗