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R N Poston

Publications and source records attributed to R N Poston.

At least 37 records · Page 2Linked to original sources
PubMed1993

The immunohistochemical heterogeneity of atheroma macrophages: comparison with lymphoid tissues suggests that recently blood-derived macrophages can be distinguished from longer-resident cells.

We studied the antigenic markers of macrophages (Mphs) in atherosclerotic human arteries by immunohistochemistry and compared them with the patterns in Mph subpopulations of tonsil and lymph node, which are also described. The staining of atheroma intimal Mphs was assessed semiquantitatively in the subendothelial, mid, and outer intima. Three patterns of reactivity with Mph antibodies were recognized. (a) Pan-Mph (antibodies HAM56, EBM11, and CD14 group). Staining was maximal in the mid-intimal zone. (b) Subendothelial Mphs (anti-muramidase, anti-alpha-1-antitrypsin and MAC387). In lymphoid tissue, sinusoidal Mphs and a few inflammatory Mphs were stained, as well as blood monocytes. This group of antibodies recognizes Mphs that are likely to be recently blood-derived (RBD-Mphs). (c) Antibodies reactive with various histiocyte populations in lymphoid tissues (anti-Factor XIII; anti-HLA Class II and LN2) also gave maximal staining in the mid-intimal zone, but differences between lesion types suggest that they are recognizing heterogeneous subpopulations of Mphs. These observations demonstrate the heterogeneity of tissue Mphs and suggest that an insight into the dynamics of tissue Mphs can be obtained from the cell phenotype. They indicate that all stages of atherosclerosis can have an outward traffic of Mphs from the blood through the arterial intima.

Antibodies, Monoclonal↗
PubMed1993

Expression of vascular cell adhesion molecule-1 in normal and inflamed synovium.

BACKGROUND: The intercellular adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) has been implicated in a number of interactions between leukocytes and cells of lymphoid and connective tissue, including endothelial cells. Such interactions within synovial tissue may be important in the pathogenesis of rheumatoid arthritis. EXPERIMENTAL DESIGN: The expression of VCAM-1 on specific cell populations in normal and inflamed synovium was investigated using a range of double-labeling techniques. RESULTS: The strongest VCAM-1 staining was found to be confined to four nonmacrophage populations (as judged in terms of CD68 expression, nonspecific esterase activity, content of prolyl hydroxylase and activity of uridine diphosphoglucose dehydrogenase): (i) type B synoviocytes, (ii) vascular wall cells outside the endothelial layer, (iii) scattered stromal cells with cytoplasmic processes, and (iv) cells resembling follicular dendritic reticulum cells in lymphoid aggregates with germinal centers (in the three samples of rheumatoid arthritic tissue where these were present). Some macrophages of the synovial intima showed weak VCAM-1 staining. Endothelial cell staining was seen but it was consistently weaker than the staining of cells of group ii. CONCLUSIONS: The four cell populations described as showing bright staining for VCAM-1 may all be involved in local interactions with leukocytes of the macrophage or lymphoid series subsequent to initial leukocyte entry into the tissue. Expression of VCAM-1 by these cells may play a role in such interactions.

Arthritis, Rheumatoid↗
PubMed1992

Immunohistochemical characterization of the cellular infiltration in asthmatic bronchi.

Bronchial biopsies obtained from 16 asthmatic patients and six normal subjects were analyzed by immunohistochemistry. In the asthmatic patients, the total numbers of macrophages infiltrating the airway mucosa were increased. Many of the macrophages had the phenotypic characteristics of blood monocytes. HLA Class II antigen was expressed on infiltrating cells and airway epithelial cells. In biopsies from the asthmatics there was a significant increase in activated eosinophils, but not in neutrophils. There was also a significant increase in the numbers of T-lymphocytes in the asthmatics, but very few B-lymphocytes were detected. These results suggest that lung macrophages may have a central role to play in the mechanisms of the chronic immune-mediated inflammatory response seen in the airway mucosa of asthmatic patients.

Adult↗
PubMed1992

Expression of intercellular adhesion molecule-1 in atherosclerotic plaques.

Immunohistochemistry of human atherosclerotic arteries demonstrates expression of the intercellular adhesion molecule-1 (ICAM-1) on endothelial cells, macrophages, and smooth muscle cells of the plaques. Normal arterial endothelial cells and intimal smooth muscle outside plaques give weaker or negative reactions; these differ from the strong endothelial expression in small vessels. Quantitative color-image analysis of the endothelial layer shows increased expression of ICAM-1 in all subtypes of atherosclerotic lesions, except fibrous plaques. Endothelial expression of ICAM-1 may be involved in the recruitment of monocytes to the lesion, as suggested by its role in the entry of leukocytes, including monocytes, into foci of inflammation. Collaboration with other mechanisms, particularly chemoattractant factors, may be important for this effect. ICAM-1 enhanced monocyte recruitment is a potential mechanism for the growth of an atherosclerotic plaque.

Arteries↗
PubMed1991

Endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 mediate the adhesion of eosinophils to endothelial cells in vitro and are expressed by endothelium in allergic cutaneous inflammation in vivo.

We have compared the adhesion of 51Cr-labeled eosinophils and neutrophils to cultured human umbilical vein endothelial cell (EC) monolayers that have been stimulated with IL-1, TNF, or LPS. Each agent stimulated the adhesion to EC of both eosinophils and neutrophils in a similar dose- and time-dependent manner. F(ab')2 fragments of mAb 1.2B6 (anti-endothelial leukocyte adhesion molecule (ELAM)-1) and mAb 6.5B5 (anti-intercellular adhesion molecule (ICAM)-1) each inhibited partially, and to a similar extent, eosinophil and neutrophil adhesion to EC monolayers prestimulated with TNF (10 ng/ml) for 6 h. Greater inhibition of both eosinophil and neutrophil adhesion was achieved by combining the effects of mAb 1.2B6 with either mAb 6.5B5 or mAb TS1/18 (anti-CD18). These observations indicate that both ELAM-1 and ICAM-1 are involved in the adhesion of eosinophils and neutrophils to EC stimulated with TNF. In order to determine whether these molecules are expressed in vivo during allergen-induced late phase allergic responses in the skin, human skin biopsies were examined at 6 h after Ag or saline challenge with the use of an alkaline phosphatase-staining technique. Both ELAM-1 and ICAM-1 were expressed with greater intensities in Ag-challenged biopsies, suggesting that these molecules may be involved in granulocyte recruitment in vivo. The similarities we have established between mechanisms of eosinophil and neutrophil adhesion to cytokine-stimulated EC suggests that factors other than differential leukocyte-EC adhesion may be responsible for the selective accumulation of eosinophils at sites of allergic inflammation.

Adult↗
PubMed1991

The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: a comparison of ultraviolet B erythema and delayed hypersensitivity.

Endothelial cell adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are cytokine-regulated cell surface molecules involved in leukocyte adhesion. We have studied two forms of cutaneous inflammation to investigate in vivo the kinetics of adhesion molecule expression in relation to tissue accumulation of leukocytes. Immunohistology was performed on skin biopsies taken from human volunteers at 1, 6, 24, 72 h, and 1 week after two minimal erythema doses (MED) of ultraviolet B (UV-B) or intra-cutaneous tuberculin-purified protein derivative (PPD) (10-100 U). ELAM-1 expression on vascular endothelium and polymorphonuclear leukocyte infiltration were first observed at 6 h and maximal at 24 h after both UV-B and PPD. At 72 h and 1 week, however, endothelial ELAM-1 was more strongly expressed in PPD biopsies. VCAM-1 was minimally expressed in control skin, and was induced above background levels on endothelium, on some perivascular cells, and on stellate-shaped cells in the upper dermis at 24 h after injection of PPD; it was maintained up to 1 week. In contrast, no induction of VCAM-1 was seen following challenge with either 2 or 8 MED UV-B. Following PPD, but not UV-B, there was marked induction of ICAM-1 expression on basal keratinocytes. In these biopsies, the inflammation induced in response to PPD therefore differed from UV-B-induced inflammation in showing prolonged expression of endothelial ELAM-1, induction of VCAM-1 on endothelium and other cells, and induction of keratinocyte ICAM-1. These differences may result from differences in the cytokines released and may in turn be responsible for the differences in the nature of the leukocytic infiltration during the two types of inflammatory response.

Cell Adhesion↗
PubMed1990

Macrophage histology in paraffin-embedded multiple sclerosis plaques is demonstrated by the monoclonal pan-macrophage marker HAM-56: correlation with chronicity of the lesion.

Using the monoclonal antibody HAM-56 with the avidin-biotin method on recent or archival paraffin-embedded tissue from multiple sclerosis brains, we have been able to distinguish between acute, chronic active and inactive lesions. HAM-56 stains all macrophages, monocytes and at least some microglia; it is the only pan-macrophage marker to our knowledge that can be satisfactorily used on conventional paraffin sections. A much narrower range of mainly perivascular macrophages in acute plaques of multiple sclerosis is stained with MAC-387, anti-muramidase and anti-alpha1-anti-trypsin. The acute plaques show HAM-56-stained macrophages throughout the lesion, and these macrophages exhibit profiles of phospholipid-rich myelinic bodies, which are also usually stainable with Luxol fast blue. Active ongoing lesions show a rim of macrophages at the edge of the lesion. These macrophages show profiles of large vacuoles, thought to represent the sudanophilic esterified cholesterol formed during demyelination. Inactive cases show none of these features; the few perivascular macrophages present often contain the end product of lipid peroxidation, ceroidlipofuscin.

Antibodies, Monoclonal↗
PubMed1989

Pathology, histochemistry and immunocytochemistry of lesions in acute multiple sclerosis.

Twenty cases of acute or early multiple sclerosis have been examined using staining, histochemical or immunocytochemical methods. They had died within 6 months after initial clinical onset (12) or commencement of an "anatomically-remote" acute relapse (8). Plaques in these acute cases showed the following characteristics: lymphocytic perivascular infiltration, plaque hypercellularity, plaque macrophage infiltration and intra-macrophage myelin debris. In most cases of clinical duration of less than 12 weeks, some macrophages showed characteristic formaldehyde-resistant markers for haematogenous macrophages (muramidase, anti-alpha 11-antitrypsin, MAC and HAM56) but, with the exception of the last, these markers subsequently declined indicating a haematogenous origin for macrophages in the early lesion. Lymphocytes were prominent in perivascular (perivenous) regions but, except in one case, were only scanty in or at the demyelinating edge of plaques. Oligodendroglial hyperplasia, indicative of remyelinating activity, was seen at the edge of plaques in one quarter of these acute cases (7 times the rate seen in chronic lesions). Astrocytic activation was not apparent in the earliest stages but was usually seen from about 6 weeks onwards. The conclusion from these observations is that the prime inflammatory process is around blood vessels with usually only scanty initial inflammatory activity in the parenchyma of the brain. Macrophages emigrating from blood vessels digest myelin either as a response to inflammatory damage to the myelin or as a response to activation signals produced in either the perivascular region or plaque.

Adolescent↗
PubMed1988

Coronary arterial dimensions and cell populations in ageing man.

A combined computerised morphometric and immunocytochemical study on the ageing human coronary arterial wall shows that dilatation of the vessel is related to age but is less related to the degree of atherosclerosis. Loss of medial smooth muscle is not related to either atherosclerosis or dilatation of the artery. Occasional cases with severe medial and adventitial infiltrates of inflammatory cells (mainly T-cells and macrophages) do develop marked ectasia, but this arteritis is rather rare and, thus, an infrequent cause of dilatation.

Aged↗
PubMed1987

The binding of immunoglobulin Fc to cationic proteins.

The interaction of cationic proteins with IgG, IgA and IgM were investigated by solid phase radioimmunoassay. All these immunoglobulins showed avid binding, IgM giving the strongest reaction, followed by IgA and then IgG. Fc fragments of IgG gave binding, but F(ab')2 fragments from the three main Ig classes did not, showing that the Fc region is the active part of the molecule. The effects of changes of ionic strength and pH are compatible with the interaction being ionic, and are similar to those seen between immunoglobulins and both Clq and cationic ion exchange gels. The addition of other serum proteins resulted in marked inhibition of the interaction. These phenomena are likely to have fundamental significance for the understanding of interactions of immunoglobulins in vivo and in vitro.

Antigen-Antibody Complex↗
PubMed1986

Diagnosing tumours on routine surgical sections by immunohistochemistry: use of cytokeratin, common leucocyte, and other markers.

Tumours of uncertain tissue of origin were investigated by immunohistochemistry on formalin fixed paraffin embedded sections. Two antibodies--PD7/26, an anti common leucocyte antigen, and CAM5.2, an anticytokeratin--recognised most lymphomas and carcinomas, respectively: 88% of these tumours were identified by the two antibodies alone. These antibodies permitted the separation of the cases into groups: positive with CAM5.2, positive with PD7/26, and a third comprising those negative with both. The negative group contained other tumours and a small number of carcinomas and lymphomas; many of the lymphomas were, apparently, of histiocytic origin. Comparison of CAM5.2 with other epithelial markers showed that it was the most effective. Some further classification of the tumours was carried out with a panel of organ and cell specific antibodies: mesotheliomas were recognised by their pattern of reactivity with epithelial markers. Overall, the tumour type was determined in 90% of cases. Immunohistochemistry performed as described can be a potent aid to the diagnostic histopathology of tumours.

Antibodies, Monoclonal↗
PubMed1985

Inflammatory vasculitis in multiple sclerosis.

Fifty-two plaque or lesion areas were examined from 25 cases of multiple sclerosis. Twenty-four of these showed acute features, whereas the rest were more chronic in nature. The acute lesions showed lymphocytic infiltration (79%), fibrinous exudation (63%), lymphocytic meningitis (50%) and venulitis (58%). Of the chronic lesions, there were only 21% with lymphocytic infiltration, 11% with fibrinous exudates, none with meningitis, 29% with organising endovenulitis, 36% with fibrosed vein walls. The finding of a fibrinous inflammatory exudate in the acute lesion is a new observation in multiple sclerosis. Likewise, the observation of an inflammatory infiltrate confined to the vein wall (and often present at a distance from the plaque) has not been previously recorded in the disease. The chronic lesion, by contrast, showed relatively little fibrin, but there was considerable reparative thickening of the walls of the involved veins. The evidence provides new humoral and cellular evidence of an inflammatory process in multiple sclerosis which precedes or is not directly associated with the demyelinating process.

Brain↗
PubMed1984

Basic proteins bind immunoglobulin G: a mechanism for demyelinating disease?

Heat-aggregated immunoglobulin G ( HAGG ) bound avidly to solid-phase basic proteins, including myelin basic protein. In contrast, monomeric immunoglobulin bound weakly. Bound HAGG could activate complement. Normal human serum strongly inhibited the binding of HAGG , even when decomplemented or greatly diluted. Cerebrospinal fluid was also inhibitory, but the effect was weaker. Apart from inhibition by decomplemented serum, the biochemical characteristics of the interaction were similar to those of other Fc ligands with IgG, particularly C1q. In multiple sclerosis this interaction could occur between IgG and central-nervous-system myelin basic protein, leading to demyelination by activation of immune mechanisms of tissue damage. Bound IgG is present in multiple sclerosis plaques and IgG from multiple sclerosis patients can produce demyelination in experimental models. However, there is little evidence of any specific immunity to central-nervous-system antigens in multiple sclerosis, and this non-specific interaction might be an important link in the pathogenesis of the disorder.

Blood↗
PubMed1983

Severe diabetic microangiopathy with normal glucose tolerance and pituitary infarction.

Blood glucose concentrations in a woman with severe retinopathy, nephropathy, and neuropathy were found to be within the normal range. A high random blood glucose concentration was recorded only once, six months before her initial presentation. At necropsy the anterior lobe of the pituitary gland showed old, extensive infarction. Occult pituitary hypofunction may explain severe diabetic microangiopathy in patients with normal glucose tolerance.

Adult↗
PubMed1983

Interactions between soluble IgG, complement and cells in lymphocyte and monocyte ADCC.

The interactions of K lymphocyte- and monocyte-mediated ADCC (antibody-dependent cell-mediated cytotoxicity) systems with monomeric and aggregated IgG in solution are compared. K-lymphocyte ADCC is inhibited by aggregate, but not by monomer, while monocyte ADCC is inhibited by both. The difference may depend on monocytes having Fc receptors of high affinity. The inhibition of K-lymphocyte ADCC by aggregates is reduced by the binding of complement to the aggregates. Adherent cells can inhibit K-lymphocyte ADCC if IgG is absent from the culture medium, but have no effect in its presence. This effect may also depend on the presence of high affinity Fc receptors on monocytes. The properties of K-lymphocyte ADCC are compatible with a significant role in vivo; by contrast monocyte ADCC is strongly inhibited by physiological concentrations of IgG.

Antibody-Dependent Cell Cytotoxicity↗