No abstract

Damage to axons in acute multiple sclerosis (MS) lesions is now well established but the mechanisms of this damage remain obscure. Here we have applied a panel of antibodies that identify cell populations and proteins contained in them with a view to detecting those cells and proteins that are localised particularly closely to damaged axons in acute, sub-acute and border-active MS plaques. Results are expressed semi-quantitatively and graphs produced that show that many of the markers show enhanced expression at sites of axon damage. However, the sharpest increase in expression in relation to axon damage was seen for Calpain I (micro-calpain), inducible nitric oxide synthase and MMP-2, suggesting that these proteins may form part of a group of proteins responsible for the initiation of myelin and/or axon damage seen in MS lesions.

BackgroundA chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain.MethodsIn this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate.ResultsThe extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface.DiscussionOur findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate.ConclusionTumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion.

Oncogenic osteomalacia (OO) is an acquired form of hypophosphataemic osteomalacia, which is associated most commonly with the development of a benign phosphaturic mesenchymal tumour mixed connective tissue type (PMTMCT). PMTMCTs are generally well vascularised tumours, and many have in the past been classified as haemangiomas and haemangiopericytomas. Although these tumours show some morphological variation, it has been proposed that they represent a distinct histopathological entity. Our aim in this study was to determine by immunohistochemistry the vascular profile of PMTMCT. Using monoclonal antibodies directed against several vascular markers, including the lymphatic endothelial cell antigens LYVE 1 and podoplanin, we found that PMTMCTs, in contrast to haemangiomas and haemangiopericytomas, contain lymphatic vessels. Taken with previous observations that PMTMCTs overexpress FGF23 and other gene products, this finding provides further evidence that most osteomalacia associated mesenchymal tumours represent a discrete pathological entity.