Volume 20, Supplement 2, 2012
Review
New insights into biological targets and therapeutic management of infectious diseases
Selleri Carmine,
Zeppa Pio,
Montuori Nunzia,
Esposito Silvano
Not available
67 kDa laminin receptor: structure, function and role in cancer and infection
Rea Vincenza Elena Anna,
Rossi Francesca W.,
De Paolis Amato,
Ragno Pia,
Selleri Carmine,
Montuori Nunzia
The 67 kDa high affinity laminin receptor (67LR) is a non integrin cell surface receptor for the extracellular matrix whose expression is increased in neoplastic cells and directly correlates with an enhanced invasive and metastatic potential. 67LR derives from homo- or hetero-dimerization of a 37 kDa cytosolic precursor (37LRP), by fatty acid acylation. Interestingly, 37LRP is a multifunctional protein involved in the translational machinery and has also been found in the nucleus, where it is tightly associated with nuclear structures.
Acting as a receptor for laminin is not the only function of this protein; indeed, 67LR also acts as a receptor for viruses, such as Sindbis virus and Dengue virus, and is involved in the internalization of the prion protein.
Here, we review the current understanding of the structure and function of this molecule, highlighting its role in cancer and infection diseases.
The urokinase-receptor in infectious diseases
Montuori Nunzia,
Selleri Carmine,
Ragno Pia
Cell migration through the extracellular matrix (ECM) or endothelial cells is a basic process in several physiological and pathological events, including the immune host response to pathogens, both in the case of innate and adaptive immunity. The urokinase-type plasminogen activator (uPA) receptor (uPAR) is a GPI-anchored cell-surface receptor largely expressed on most of leukocytes, including monocytes/macrophages, granulocytes, immature dendritic cells. uPAR has been detected also in soluble and cleaved forms, which are increased in several pathologies.
uPAR focuses the proteolytic activity of its ligand, the serine-protease uPA, on the cell membrane, thus promoting localized plasminogen activation and allowing the cell to degrade surrounding ECM and to move across physical barriers. However, the discovery that uPAR can bind with high affinity a component of the ECM, vitronectin (VN), and associates to cell surface molecules to activate signalling pathways inside the cells, largely expanded the role that uPAR can play in cell proliferation/survival and adhesion/migration, which are crucial events for an efficient immune response to infectious agents. This review is focused on the expression and possible functions of the various forms of uPAR in infectious diseases.
Hp(2-20) peptide of Helicobacter pylori and the Innate Immune Receptors: Specific Role(s) of the Formyl Peptide Receptors
Rossi Francesca W.,
Prevete Nella,
Montuori Nunzia,
Ragno Pia,
Selleri Carmine,
Marone Gianni,
De Paolis Amato,
Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative bacterium that affects more than half of the world’s population. H. pylori has co-evolved with humans to be transmitted from person to person and to persistently colonize the stomach. A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases. During its long coexistence with humans, H. pylori has evolved complex strategies to limit the degree and extent of gastric mucosal damage and inflammation as well as immune effector activity. In this complex strategy an important role is played by the interaction of H. pylori with a specific class of innate immune receptors, named N-formyl peptide receptor family (FPRs). In the last years several virulence factors have been studied in an effort to correlate bacterial phenotype with specific gastric manifestations and to clarify the pathogenetic mechanisms. Several peptides produced by H. pylori appear to be involved in inflammation associated with the infection. A particular interest has been focused on the Hp(2-20) peptide derived from the bacteria.
Thus, aim of the article is to comment on some advances in the elucidation of specific interactions between the Hp(2-20) peptide and FPRs.
Original article
Low-dose valgancyclovir as cytomegalovirus reactivation prophylaxis in allogeneic haematopoietic stem cell transplantation
Serio Bianca,
Rosamilio Rosa,
Giudice Valentina,
Pepe Stefano,
Zeppa Pio,
Esposito Silvano,
Pezzullo Luca,
Rocco Monia,
Montuori Nunzia,
Selleri Carmine,
The efficacy and safety of low dose oral valgancyclovir (VGCV) as cytomegalovirus (CMV) reactivation prophylaxis was retrospectively evaluated in 32 consecutive patients which underwent allogeneic HLA-matched related and unrelated hematopoietic stem cell transplantation (HSCT).
Thirty HSCT recipients showed pretransplant CMV seropositivity. Fifteen received a myeloablative conditioning regimen, while seventeen patients received a reduced-intensity conditioning regimen. Twenty-one patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporin A (CsA) and methotrexate (MTX), and the others CsA with MTX and anti-thymocyte globulin. CMV infection was monitored weekly using polymerase chain reaction (PCR). VGCV was administered orally at a dose of 450 mg daily for six months. Six patients developed a positive CMV-PCR on average 56 days after HSCT successfully treated with VGCV at 1800 mg/day, except one who developed fatal gastrointestinal CMV disease. At the time of CMV reactivation, four patients had been affected by grade II-IV acute GVHD and two by an extensive chronic GVHD. No significant specific VGCV-related toxicity was encountered. Seven patients presented hematological toxicity which did not require drug discontinuation.
Our data suggest that low dose VGCV is safe and effective as CMV reactivation prophylaxis in allogeneic HSCT recipients. These results require further validation in prospective randomized studies.
Non lymphomatous clonal B-Cell populations in enlarged lymph nodes in acquired immunodeficiency syndrome.
Cozzolino Immacolata,
Vigliar Elena,
Sosa Fernandez Laura Virginia,
Selleri Carmine,
Pepe Stefano,
Vitale Mario,
Triggiani Massimo,
Zeppa Pio
Clonal B-cell populations in non-lymphomatous processes have been sporadically reported in enlarged reactive lymph nodes and mucosa-associated lymphoid cell populations. These generally small clones are considered non-malignant proliferations of B-lymphocytes determined by an abnormal response to bacterial or viral antigen stimulation. In cases reported in literature, clonality was detected by light chain assessment and or by polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain (IgH) gene in histologically and clinically proven non lymphomatous processes. In this study the clinical, cytological, phenotypical and pathological features of three HIV patients in which non-lymphomatous clonal B-cell populations detected in enlarged lymph nodes are reported. All the patients complained for later cervical lymph nodes enlargement, positive at the FDG-positron emission tomography scan. Fine needle cytology, coupled with flow cytometry showed atypical lymphoid cell proliferations and kappa (2 cases) or lambda (1 case) light chain restriction. Reactive, non lymphomatous nature of these processes were then proven by histological control in two cases and by clinical follow-up in the last one; corresponding clinical and pathological aspects are discussed. Clonal B-cell populations in non-lymphomatous processes can sporadically occur in enlarged reactive lymph nodes in immunodeficiency as well as in autoimmune processes. Awareness of the phenomenon and attention should be paid in the evaluation of corresponding pathological features and in the clinical management of corresponding patients.
Case report
Successful management of pulmonary mucormycosis with liposomal amphotericin B and surgery treatment: a case report.
Serio Bianca,
Rosamilio Rosa,
Giudice Valentina,
Zeppa Pio,
Esposito Silvano,
Fontana Raffaele,
Annunziata Silvana,
Selleri Carmine
Mucormycosis is an increasingly recognized invasive fungal infection (IFI) in patients with acute myeloid leukemia (AML) and after allogeneic (allo) stem cell transplantation (HSCT); it is mainly due to the severe and prolonged neutropenia related to high-dose chemotherapy. In such patients, the lung is the most frequently involved site in mucormycosis. Since rapidly progressive dissemination may occur after pulmonary mucormycosis in hematologic malignancies, early diagnosis and prompt initiation of an effective antifungal therapy is mandatory for a successful outcome.
We report the case of a young AML patient who developed, early after the onset of neutropenia in the first induction phase of chemotherapy, a rapidly progressive pulmonary IFI, successfully treated with liposomal Amphotericin-B (LAmB) and then with a limited open toracothomy biopsy, clearly establishing diagnosis of mucormycosis and removing lung infiltrate. Secondary prophylaxis with LamB, applied during both consolidation therapy and myeloablative sibling allogeneic HSCT, was effective to prevent IFI recurrence despite the development of grade I acute graft-versus-host disease (GVHD) and limited chronic GVHD requiring immunosuppressive treatment.
Our case report further provide evidence that the combined surgical and LAmB therapy is an effective and safe choice for the management of pulmonary mucormycosis in hematological immunocompromised patients.
