Neutrophils act as a first line of defense against bacterial and fungal infections, but they are also important effectors of acute and chronic inflammation. Genome-wide association studies have ...established that the gene encoding the protein tyrosine phosphatase nonreceptor 22 (PTPN22) makes an important contribution to susceptibility to autoimmune disease, notably rheumatoid arthritis. Although PTPN22 is most highly expressed in neutrophils, its function in these cells remains poorly characterized. We show in this article that neutrophil effector functions, including adhesion, production of reactive oxygen species, and degranulation induced by immobilized immune complexes, were reduced in Ptpn22
neutrophils. Tyrosine phosphorylation of Lyn and Syk was altered in Ptpn22
neutrophils. On stimulation with immobilized immune complexes, Ptpn22
neutrophils manifested reduced activation of key signaling intermediates. Ptpn22
mice were protected from immune complex-mediated arthritis, induced by the transfer of arthritogenic serum. In contrast, in vivo neutrophil recruitment following thioglycollate-induced peritonitis and in vitro chemotaxis were not affected by lack of PTPN22. Our data suggest an important role for PTPN22-dependent dephosphorylation events, which are required to enable full FcγR-induced activation, pointing to an important role for this molecule in neutrophil function.
Integrins are a family of transmembrane proteins that allow communication between the extracellular matrix and the interior of cells. Chondrocytes, cells of articular cartilage, express integrins and ...these molecules appear to have a variety of roles including mechanotransduction. Integrins are known to associate with a number of accessory molecules such as CD147 that may act to regulate their activity. The purpose of this study was to investigate the expression of CD147 in normal and osteoarthritis human articular cartilage and identify potential roles in mechanical signalling.
Expression of CD147 in normal and osteoarthritis human articular cartilage was examined by the immunostaining and Western-blotting techniques. Potential roles in mechanotransduction were studied by assessing effects of function blocking antibodies on the electrophysiological response to mechanical stimulation.
CD147 was extensively expressed by chondrocytes in normal and osteoarthritic cartilage and shown by Western-blotting to have a molecular weight in the region of 35-50 kDa. Function blocking antibodies had no effect on the membrane depolarisation response of chondrocytes from osteoarthritic cartilage to mechanical stimulation.
Human articular chondrocytes show extensive expression of CD147 in normal and osteoarthritic cartilage. Roles for this molecule in regulation of chondrocyte function remain to be defined.
Pathology of soft tissue tumours Oniscu, Anca; Salter, Donald
Surgery (Oxford),
09/2016, Letnik:
34, Številka:
9
Journal Article
Recenzirano
Abstract Soft tissue tumours are a heterogeneous group of neoplasms with differentiation towards mesenchymal tissue. They may arise anywhere in the body and show similar clinical presentation. ...Traditional histopathological diagnosis is now complemented by molecular diagnostic techniques that have become firmly established ancillary diagnostic methods. This article provides a short overview of the aetiology and clinical features of soft tissue sarcomas with an update on how molecular genetics is influencing classification and management of these rare tumours.
OBJECTIVE The objective of this study was to detail the topographical and zonal distribution of α and β subunits of the integrin superfamily in normal and osteoarthritic cartilage. METHODS ...Immunohistochemistry utilising antibodies towards α and β subunits was performed on cryostat sections of human articular cartilage from macroscopically normal (n = 6) and osteoarthritic (n = 6) femoral heads. Samples of articular cartilage were obtained from 12 topographically distinct sites from each femoral head. Each section was divided into zones (superficial, middle, deep) and staining scores were recorded. RESULTS Normal cartilage stained for integrin subunits α1, α5, αV, β1, β4, and β5, but not for α2, α3, α4, α6, β2, β3, and β6. Intact and non-intact residual cartilage from osteoarthritic femoral heads stained for α1, α2, α5, αV, β1, β4, and β5. Staining was occasionally seen for α4 and β2, but not for α3, α6, β3, and β6. There was no topographical variation in the staining for any of the subunits in either normal or osteoarthritic cartilage. The only subunit that displayed a zonal variation was αV; staining for this subunit was most pronounced in the superficial zone compared with the middle and deep zones. CONCLUSION Chondrocytes in normal and osteoarthritic cartilage express the integrin subunits α1, α5, αV, β1, β4, and β5. Chondrocytes in osteoarthritic cartilage, in addition, express the α2, α4, and β2 subunits. The αv subunit is expressed by more chondrocytes in the superficial zone in comparison with cells in the deeper zones. None of the subunits display topographical variation in expression.
We report a case of a 27-year-old man who presented with a progressive painful swelling at the base of his left index finger, with radiographs and a computed tomography scan revealing a lytic lesion ...of the proximal phalanx. Following further investigation, the patient underwent a bone biopsy that revealed a florid noncaseating granulomatous chronic inflammatory infiltrate, compatible with sarcoidosis. Osseous sarcoidosis of the hand is uncommon and, in the absence of significant systemic disease, is rarely the primary presenting feature. Early diagnosis and treatment of such undetermined bone pathology, via referral to a regional musculoskeletal tumor service, can prevent significant future complications.
To test whether radio-frequency analysis of coronary plaques predicts the histological classification, r.f. data were collected using a 30 MHz intravascular ultrasound scanner. Two hundred ...ninety-nine regions-of-interest from eight postmortem coronary arteries were selected and identified by histology as falling into one of seven different tissue types. These are loose fibrous tissue (
n = 78), moderate fibrous tissue (
n = 27), dense fibrous tissue (
n = 33), microcalcification (
n = 14), calcified plaque (
n = 55), lipid/fibrous mixture (
n = 51) and homogeneous areas of lipid pool (
n = 29). On the basis of a previous study, four spectral parameters were calculated for each of the regions-of-interest: maximum power (dB), mean power (dB), spectral slope (dB/MHz) over the bandwidth 18–35 MHz and the intercept of the spectral slope with the 0 Hz axis (dB). A minimum-distance classifier using the
Mahalanobis (1948) distance was applied to the data. Following resubstitution of the training data into the classifier, the total correctly classified was 54%. The data were reclassified using three broader tissue groups: (1) calcified plaque, (2) lipid pool and (3) a mixed fibrous category, incorporating loose fibrous tissue, moderate fibrous tissue, dense fibrous tissue, lipid/fibrous mixture and microcalcification. The total correctly classified was 86%. Using “leave-one-out” cross-validation, the classification rates were 48% for seven tissue subgroups and 83% for three broader categories of tissue type.
Signal regulatory proteins (SIRP) belong to immunoglobulin super family (IgSF) and relate to integrin signaling cascades. It has been shown that SIRPalpha is expressed in a variety of cells including ...myeloid cells and neurons. In the present study the expression of this IgSF member in articular chondrocytes was investigated.
Using a panel of anti-SIRPalpha antibodies, immunohistochemistry, Western-blotting and electrophysiology methods, expression of SIRPalpha and its role in chondrocyte mechano-transduction were assessed.
No identifiable positive signal was obtained by using immunohistochemistry methods on frozen and paraffin sections. SIRPalpha is expressed by both normal and osteoarthritis cultured chondrocytes. The electrophysiological response of chondrocytes in the presence of SE7C2 mAb was significantly inhibited whereas; SE5A5 did not show any modification in this response.
It seems likely that SIRPalpha could be associated with other proteins such as integrins, CD47 and ion channels, which contribute to the electrophysiological response of human articular chondrocytes. In any case, this study has provided a specific functional role for SIRPalpha in chondrocyte mechano-transduction.
Glucocorticoid therapy, especially at higher doses, is associated with significant adverse side effects including osteoporosis. Leptin, secreted from adipose tissue, has diverse effects on bone ...tissue regulation. As glucocorticoids stimulate leptin synthesis and secretion directly in adipose tissue we hypothesised that dexamethasone (DEX) induced osteoporosis may, in part, be mediated by an osteoblast dependent leptin-leptin receptor pathway. Human bone cells expressed leptin and leptin receptors (Ob-Ra and Ob-Rb). DEX increased leptin, Ob-Ra and Ob-Rb expression in a dose-dependent manner while decreasing expression of osteocalcin. In the presence of leptin, Cbfa1 and osteonectin expression showed no significant change, whereas osteocalcin expression was decreased. Recombinant human quadruple antagonist leptin suppressed DEX-induced osteocalcin downregulation. The signaling pathway involved up-regulation of JAK2. In conclusion, upregulation of leptin and Ob-Rb in human bone cells by DEX is associated with down-regulation of osteocalcin expression. The down regulation of osteocalcin by DEX was partially through a leptin autocrine/paracrine loop. Adverse effects of DEX on the skeleton may be modified by targeting leptin signaling pathways.
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