Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis

<p>Abstract</p> <p>Background</p> <p>Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls.</p> <p>Methods</p> <p>Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MC_Tand MC_TCmast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β.</p> <p>Results</p> <p>In the alveolar parenchyma in lungs from patients with CF, MC_TCnumbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MC_TCand MC_Tcells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MC_TCdensity was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MC_TCcorrelated positively with the degree of fibrosis. The increased density of MC_TC, as well as MC_TCexpression of TGF-β, correlated negatively with patient lung function.</p> <p>Conclusions</p> <p>The present study reveals that altered mast cell populations, with increased numbers of MC_TCin diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.</p

LYMPHOLOGY

The migration routes of lymphocytes through high endothelial venules (HEVs) of control and hypertrophic pharyngeal tonsil (HPT) tissue sections were investigated by immunohistochemistry using the expression of a hormone [calcitonin (CT)] and two calcium-dependent endothelial adhesion molecules (E-selectin and P-selectin), as well as electron microscopy. A marked increase in CT-specific staining was observed in the endothelial cells of HE V in the HPT group compared to the control group. Expressions of E-selectin and P-selectin on HEVs of control group were faint, when compared to the strong expression of these selectins on HEVs of HPT. Electron microscopically, we demonstrated that lymphocytes transmigrated through HEV and observed the close membranous contact between endothelial cells and lymphocytes during this process. We speculate that increasing CT during inflammation may be important for lymphocyte migration through the HEVs via controlling the expression of E-selectin and P-selectin

CLINICAL RHEUMATOLOGY

Scleroderma is a connective tissue disorder characterised by excessive accumulation of collagen in the skin and internal organs. The most likely explanation for this process is local activation of collagen synthesis from fibroblasts. Our intention was to elucidate whether TGF-beta(3) and mast cells play a pathogenic role in abnormal connective tissue formation in scleroderma. In this study, skin biopsies from 20 patients with scleroderma and five from healthy individuals were studied by an indirect immunoperoxidase technique to determine the immunoreactivity of TGF-beta(3) in the dermis. In addition, skin samples were stained with toluidine blue to count the number of mast cells in scleroderma, and tissues were examined under the electron microscope to evaluate the ultrastructural changes. Increased TGF-beta(3) immunoreactivities were detected in the dermis in the patient's skin, suggesting the presence of a subpopulation responsible for the increased collagen production. Mast cell counts in the skin of patients with scleroderma were significantly greater (19.2 +/- 4.1/unit) than those of normal controls (4.4 +/- 1.2/unit). Ultrastructural observations indicated that there is a close relationship between the mast cells and fibroblasts. These results suggest that fibrosis in scleroderma could evolve through the activation of fibroblasts and the regulatory mechanisms that appear to modulate the behavior of these cells with respect to collagen production

JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY

The antigen presenting cells (APCs) with special interest to dendritic cells (DC), were investigated in 28 hypertrophic and 10 control pharyngeal tonsils of children by histochemistry, immunohistochemistry and electron microscopy. In this study, we are trying to clarify the function and classification of APC in pharyngeal tonsils using morphologic criteria, Human Leukocyte Antigen Monoclonal Antibody (HLA-DR MoAb), which is specific for APCs, and acid phosphatase (APh) reacting with both phagosomes and lysosomes. The surface epithelium of the patient group examined by light microscopy, heavy infiltration of lymphocytes, degenerated columnar cells and a few 14LA-DR MoAb (+) columnar cells was observed. Additionally, a significant number of APCs which were Langerhans cells (LCs), interdigitating dendritic cell (IDC), follicular dendritic cell (FDC) and macrophages were stained with both HLA-DR MoAb and APh in the epithelial, interfollicular-subepithelial and follicular areas. Ultrastructural examinations revealed that lymphocytes, macrophages, LC and M cells were found among the surface columnar epithelial cells of the patient group. The interactions between M cells and LC suggested that M cells probably passed antigens from surface to LC. In the interfollicular-subepithelial areas of the hypertrophic pharyngeal tonsil, IDCs were in close contact with lymphocytes, macrophages and plasma cells. Seven types of FDCs (FDC-1 - FDC-7) were recognised according to their ultrastructural appearances. Differentiated FDCs (FDC-4) were also in close contact with each active subtype of FDCs in follicular areas besides lymphocytes. These findings supported the idea that although the pharyngeal tonsils contained several types of active APCs, only DC were in close contact with immunocompetent cells and the other APC's. Therefore, these morphologic appearances of DC could be a sign of function to initiate the immune response of the pharyngeal tonsil

ANALYTICAL AND QUANTITATIVE CYTOPATHOLOGY AND HISTOPATHOLOGY

Objective: To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. Study Design: Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mices pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. Results: In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p<0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p<0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p<0.005). Conclusion: COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium

ANALYTICAL AND QUANTITATIVE CYTOPATHOLOGY AND HISTOPATHOLOGY

OBJECTIVE: To investigate the reaction of versican and heparin-binding EGF-like growth factor (HB-EGF) molecule concentrations to acute radiation exposure in normal bladder and rectal tissue samples in order to gain more insight into the effects of cancer radiotherapy. STUDY DESIGN: Four groups with 6 male adult Swiss Albino mice per group were investigated. The mice bladder and rectum tissue samples were subjected to a 10-Gy single-dose radiation exposure in the pelvic region with a Co-60 teletherapy device and investigated 1, 2, and 7 days after radiation exposure, with 1 reference group which was not exposed to radiation. RESULTS: In the immunohistochemical examination of the tissue samples with anti-versican and anti-HB-EGF primary antibodies was observed a statistically significant increase 7 days after radiation exposure. CONCLUSION: The observed increase of versican and HB-EGF concentrations in the normal tissue matrix after radiation exposure may play a role in the side effects of radiotherapy

EUROPEAN JOURNAL OF INFLAMMATION

Objective: Patients who have had pelvic radiotherapy as part of their cancer therapy may develop subsequent urinary bladder injury. The acute changes that the urothelium undergo after radiation are known, but the healing mechanism of the urothelium of the urinary bladder after pelvic radiotherapy is not clearly understood. Proopiomelanocortin (POMC) peptides, which have immunomodulatory effects, are produced locally in sites outside of the central nervous system. This study aims to determine the role of POMC expression in the urothelium during radiation injury. Methods: Twenty-four male Swiss Albino mice were divided into four groups. A single-fractioned 10 Gy of ionizing radiation was applied to the pelvic zone of all mice with Cobalt-60 radiotherapy. The first group 1, which consisted intact animal and not irradiated was the control group, and the second, third, and fourth groups were euthanized after 24 h (Group 2), 48 h (Group 3), and 7 days (Group 4) after irradiation. All bladders were prepared for histochemical analysis using hematoxylin eosin (H&E) and immunohistochemical analysis using anti-POMC antibody. Results: No morphological differences were seen in all the group samples stained with H&E. POMC expression of the urothelium of bladder tissue samples shows different staining levels. Group 1 (96.7 +/- 7.68), Group 2 (88.3 +/- 8.04), and Group 3 (85.10 +/- 10.9) were very weakly stained, but the POMC immunoreactivity of Group 4 (113.0 +/- 12.8) was observed to be strong. Conclusion: Expression of POMC from urothelium seems to prevent bladder damage from radiation supplying differentiation and restoration of the urothelium

EARLY CLINICAL AND ULTRASTRUCTURAL EFFECTS OF DILTIAZEM INJECTION ON RABBIT EXTRAOCULAR-MUSCLES

WOS: A1995TH74900009PubMed ID: 8751343We injected diltiazem into the left lateral rectus muscles (LR) of 10 rabbits in order to examine the ultrastructural effects of diltiazem on rabbit extraocular muscles and estimate its advantages in clinical use as an alternative to the surgical therapy of strabismus. The animals were divided into two groups according to the time of evaluation following the injection. The LR muscles of both eyes of the first group were respected 60 min after the injection, for ultrastructural examination. The same procedure was done for the second group at the 24th hour The right eyes were used as the control group. There was a medial shift 3-5 min following the injection in the left eyes of both groups. The ultrastructural examination revealed weakness in muscle contractility, probably as a result of inhibition of glycogen usage due to calcium accumulation. In this study, we examined the early clinical and ultrastructural effects of diltiazem