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C Sorg

Publications and source records attributed to C Sorg.

At least 145 records · Page 8Linked to original sources

Cellular events associated with inflammatory angiogenesis in the mouse cornea.

The aim of this study was to establish an angiogenesis model in the mouse and to define immunohistochemically the cellular events that precede angiogenesis. After chemical cauterization of the murine cornea, neovascularization was observed within 36 hours. The cellular infiltrate was analyzed by using antibodies on cryostat and paraffin sections and by histochemical staining for mast cells. It was found that neither T lymphocytes nor mast cells nor macrophages in a more mature stage of development were part of the infiltrate that preceded the ingrowth of new blood vessels. Instead, the infiltrating cells appearing from 3 hours on were granulocytes and inflammatory monocytes, as detected by an antibody against the calcium-binding protein MRP14. The authors conclude that the induction of angiogenesis during nonspecific inflammation is associated with the early influx of myelomonocytic cells, but not with the infiltration of mature macrophages, T lymphocytes, or mast cells. This study shows that immunohistochemical analysis of cauterized murine corneas presents a useful tool for further studies on cells and cell products involved in the angiogenic process.

Animals↗

Detection of migration inhibitory factor (MIF) by a monoclonal antibody in the microvasculature of inflamed skin.

Macrophage migration inhibitory factor (MIF) is known as a mediator of cellular immunity with specific effects on the differentiation of mononuclear phagocytes. There is little information on the production of MIF in vivo and its role in the pathophysiology of inflammation. We studied the distribution of MIF in various tissues with a monoclonal antibody against human MIF (1C5/B) using the indirect immunoperoxidase method. Here, we investigate the expression of MIF on endothelial cells of dermal vessels. Our results show that dermal vessels may constitutively express MIF and can be strongly activated to express MIF in acute inflammations such as eczema and psoriasis in contrast to the chronically infiltrated skin from patients with pseudolymphomas and sarcoidosis. In these cases a possibly MIF defective state of vessels and a restriction of positive vessels to distinct anatomical sites of the inflamed skin was detected. The significance of the described association of MIF with vascular endothelium is still a matter of speculation. MIF expression on endothelium may provide an important differentiogenic signal for mononuclear phagocytes on their way to the tissue site.

Antibodies, Monoclonal↗

Macrophage subsets in different types of urticaria.

Biopsy specimens from lesional and uninvolved skin of nine patients with delayed pressure urticaria, three patients with acute urticaria, six patients with chronic recurrent urticaria, and four patients with urticaria pigmentosa were analyzed by routine histology and by immunochemistry for their reactivity with monoclonal antibodies to three different subsets of macrophages. Skin from 12 healthy volunteers served as control. Uninvolved skin of patients did not differ from that of healthy volunteers. An antibody against activated macrophages (27E10) was reactive to a marked extent with macrophages in wheals of pressure urticaria, more variably in acute and chronic urticaria, and practically not at all in urticaria pigmentosa. Antibodies with specificities for macrophages in healing (RM3/1) and normal (25F9) tissue reacted more markedly in all but pressure urticaria lesions, compared with normal skin. These findings indicate an active involvement of inflammatory macrophages in whealing reactions while these cells play apparently no role in cutaneous mast cell proliferation (urticaria pigmentosa).

Adult↗

Localization of apolipoprotein E in normal and atherosclerotic human aorta.

To elucidate the role of apolipoprotein E (apo E) in atherogenesis, we have investigated the localization of apo E in normal and atherosclerotic aortas as well as in other tissues of 32 post-mortem individuals. Using double immunofluorescence it has been found that normal intima of individuals older than 20 years and some adolescents contained immunoreactive material that reacted with poly- and monoclonal antibodies to apo E. A staining pattern of apo E differed from that of apolipoprotein B, the latter being seen in normal intima of each child older than 7 years. Apo E was present extracellularly in lipid streaks and atheromatous plaques, where its staining was particularly intensive around the necrotic zone of plaques. Some macrophages in the plaques of 4 aortas exhibited apo E-positive staining, while aortic endothelial and smooth muscle cells never contained apo E. Apo E-positive staining was not found in the majority of vessel cells, it was always, however, observed in other types of cells including hepatocytes. Kupffer cells, spleen macrophages and cerebral astrocytes. Our findings indicate that only some macrophages in human aorta may be responsible for the production of apo E that can participate in reverse cholesterol transport. At the same time, apo E accumulation in the aortic wall may promote the development of atherosclerosis.

Adolescent↗

Phenotyping of macrophages with monoclonal antibodies in endomyocardial biopsies as a new approach to diagnosis of myocarditis.

Cryostat sections of endomyocardial biopsies from 53 patients (mean age 41 +/- 5 years, 38 male and 15 female) clinically indicated to suffer from myocarditis were stained using monoclonal antibodies against subpopulations of T-lymphocytes and macrophages and with polyclonal rabbit-anti-human sera marking two calcium-binding proteins expressed by monocytes and macrophages appearing in inflammatory sites only. No inflammatory infiltrate cells were found in 13 cases (25%). Mononuclear cell infiltrates were present in 40 cases (75%). Ten biopsies showed a predominance of macrophages bearing the marker 27E10, characteristic for an early acute inflammation and 18 biopsies contained 25F9 positive macrophages, characteristic for a late stage of inflammation. An intermediate type of inflammation with both macrophage types present was found in 12 patients. Patients with immunohistologically confirmed myocarditis had atrial, ventricular or combined forms of arrhythmias (78%), scars in the vectorcardiogram (100%) and radiological evidence of cardiomegaly (36%). In conclusion, typing and endomyocardial biopsies for macrophage subpopulations is a sensitive new approach to assess the diagnosis of myocarditis.

Adult↗

Expression of basic fibroblast growth factor (bFGF) in Kaposi's sarcoma: an immunohistologic study.

Ten cases of Kaposi's sarcoma (KS) including five AIDS-KS, one classical KS, and four pseudo-KS (acroangiodermatitis) were investigated for their expression of basic fibroblast growth factor. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections with affinity-purified anti-bFGF antibodies. It was found that bFGF was strongly expressed in basal and suprabasal keratinocytes, which were also intensively stained in normal skin biopsies. The growth factor was generally absent from the endothelial cells and spindle cells of the neoplasms. These cell types exhibited a very faint staining in a small number of lesions. The studies provide strong evidence that proliferation of KS tumor cells may not be explained by autocrine secretion mechanism of the growth factor, which has been suggested in previous reports with in vitro cultured KS cell lines.

Acquired Immunodeficiency Syndrome↗

Presence and distribution of leucocyte subsets in the murine epididymis after vasectomy.

Male mice were vasectomized by 'open-ended' or 'closed' techniques. After 4 weeks the cell-mediated immune reactions were compared with those of sham-operated animals by immunohistochemical localization of leucocytes, using specific monoclonal antibodies. Macrophages and MHC class II antigen-positive cells were the major cell types to appear in all regions of the epididymis after both types of operation. There was recruitment of T-helper/inducer leucocytes but not of T-suppressor-cytotoxic cells. An increased presentation of macrophage-migration inhibiting factor antigen appeared in interstitial and peritubular locations. After 'closed' and 'open-ended' vasectomy granulomata developed in the epididymis. The sperm-containing lumen of these granulomata was invaded by macrophages, MHC class II-positive cells and T-helper/inducer lymphocytes. This mouse model thus reveals a significant epididymal inflammatory response of the epididymis to vasectomy.

Animals↗

Glucocorticoid-induced appearance of the macrophage subtype RM 3/1 in peripheral blood of man.

The effect of intravenous administration of the glucocorticoid prednylidene on the macrophage subtype RM 3/1 in the peripheral blood of man was studied. Injection of 60 mg steroid resulted in an increase in the proportion of RM 3/1 positive monocytes 12 h after application from the basic level to about 80%. After 24 h the number of RM 3/1 positive cells decreased but remained elevated over the basis rate for a period of at least 15 days. Similar results were obtained after administration of 30 or 6 mg prednylidene even if the peak value occurred with a delay of 12 h after 6 mg. A dose- and time-dependent induction of the RM 3/1 positive subtype could also be demonstrated in vitro by the addition of prednylidene or dexamethasone to cultured purified human monocytes/macrophages. Deoxycortone or indomethacin had no effects. These results suggest that glucocorticoids exert their influence on cells of the mononuclear phagocytic lineage by inducing a distinct monocyte/macrophage subpopulation which seems to be associated with anti-inflammatory functions.

Adult↗

Differences in migration inhibitory factor production by C57Bl/6 and BALB/c mice in allergic and irritant contact dermatitis.

Two strains of mice, BALB/c and C57Bl/6, which are known to differ in their inflammatory responsiveness to allergens, were analyzed regarding their expression of macrophage migration inhibitory factor (MIF). Allergic contact dermatitis to 2,4-dinitro-1-fluorobenzene and irritant contact dermatitis to croton oil were studied immunohistologically at designated time intervals after elicitation. BALB/c mice presented a significantly more intense ear swelling response than C57Bl/6 mice and showed a strong endothelial MIF expression in the early phase of inflammation in both allergic and irritant contact dermatitis. Endothelial MIF expression was much weaker in C57Bl/6 mice. Furthermore, the infiltration rate of inflammatory cells (MIF+ and BM8+ macrophages, Lyt2+ and L3T4+ T cells) was significantly higher in BALB/c than in C57Bl/6 mice. We conclude that genetically determined differences of susceptibility to allergens and irritants in BALB/c and C57Bl/6 mice are reflected by the intensity of MIF expression in the microvascular endothelium and immigrating inflammatory cells. MIF seems to appear as first molecular equivalent of developing inflammation and probably determines the degree of cellular infiltration.

Animals↗

Expression of intercellular adhesion molecule-1 in murine allergic contact dermatitis.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the interaction of immunocompetent cells in inflammation. It contributes to lymphocyte recruitment, antigen presentation and T-cell activation. Recently, the murine homologue of ICAM-1, originally designated as MALA-2, has been identified. The monoclonal antibody YN1/1.7 for murine ICAM-1 enables the analysis of ICAM-1 expression in murine allergic contact dermatitis, a prototype of cutaneous T-cell-mediated inflammatory response. At 0, 1, 8, 24, 48, 72 h, and 7 and 14 days after challenge with 2,4-dinitrofluoro-1-benzene (DNFB) cryostat sections of ear skin were immunostained for ICAM-1, I-A and mononuclear cells (L3T4, Lyt-2, BM8). In normal skin ICAM-1 labeling was restricted to endothelial cells and dermal dendritic cells/macrophages; keratinocytes (KCs) did not express ICAM-1. The dermal cellular infiltrate increased progressively from 8 to 72 h after DNFB challenge. The majority of infiltrating cells were BM8+ macrophages (75%) and L3T4+ (10%) or Lyt-2+ T cells (10%); maximally 30% of those stained positive for ICAM-1. At 24 h, focal ICAM-1 expression on KCs developed, reached a maximum at 72 h and faded thereafter. Migration of T cells into the epidermal layer started at 48 h at sites which had already expressed ICAM-1. Our data provide evidence that expression of ICAM-1 by epidermal cells precedes infiltration of the epidermis by T lymphocytes as shown before in human cutaneous disorders. Thus, a mouse model may be useful to investigate the role of ICAM-1 in inflammation further.

Animals↗

In situ detection of basic fibroblast growth factor by highly specific antibodies.

Basic fibroblast growth factor (bFGF) is thought to be of major importance for fibrosis and angiogenesis. Despite intensive studies dealing with the biochemistry and multiple biologic effects of bFGF, the cellular distribution is virtually unknown. Therefore, using the indirect immunoperoxidase technique, we examined the effect of bFGF on a large pattern of normal, inflammatory, and tumorous human tissues. Staining was performed on cryostat sections with a highly specific affinity-purified antiserum. In normal tissues, especially those of the thymus and placenta, mainly dendritic cells contained the growth factor. High levels of bFGF were also detected in basal cells and gland epithelial cells of skin biopsies. A conspicuous expression was observed in chronic inflammatory tissues corresponding to a generally pronounced proliferation of fibroblasts and endothelial cells in these situations. Tumors revealed a very heterogenous staining pattern. In some lesions, bFGF was predominantly present in infiltrating and endothelial cells. In several, neoplasms tumor cells exhibited an intensive staining. In some, especially vascular tumors, bFGF could not be detected. From the staining results it is concluded that angiogenesis is not simply controlled by the presence of bFGF but is mediated by a balance of several angiogenic inducers and inhibitors.

Blood Cells↗

Immunohistochemical detection of bFGF and TNF-alpha in the course of inflammatory angiogenesis in the mouse cornea.

Tumor necrosis factor alpha (TNF-alpha) and basic fibroblast growth factor (bFGF) have been assigned a major role in the induction of angiogenesis. By performing immunohistochemical studies of cauterized mouse corneas, the in situ distribution of bFGF and TNF-alpha in the course of inflammatory neovascularization was investigated. bFGF was found throughout the corneal epithelium of untreated and cauterized eyes. However it was only rarely detected in the endothelium or in infiltrating cells before the onset of neovascularization. TNF-alpha was not expressed by any cell before the ingrowth of new blood vessels, which took place within 36 hours after cauterization. It is concluded that the release of these cytokines by infiltrating cells is of minor or no importance for the induction of sterile inflammatory angiogenesis.

Animals↗

The cytogenesis of macrophages and osteoclast-like giant cells in bone tumors with special emphasis on the so-called fibrohistiocytic tumors.

Recent investigations have suggested that osteoclasts and osteoblasts belong to different cell systems: osteoclasts originate from hemopoietic stem cells, most probably via precursors of the mononuclear phagocyte system. Osteoblasts, however, arise from local mesenchyme. The present classification of bone tumors issued by the WHO, however, is still based on the assumption of osteoclasts and osteoblasts being merely different manifestations or differentiations of the same basic cell type. Consequently, histiocytes or macrophages as well as osteoclast-like giant cells are interpreted in most bone tumors as an autochthonous component of the tumor. In the present study, this theory is contradicted by histological immunohistological, electron microscopic, and autoradiographic-electron microscopic results on a larger number of osteosarcomas, chondromas, chondrosarcomas, chondroblastomas, aneurysmal bone cysts, giant cell tumors of bone, malignant fibrous histiocytomas, fibrosarcomas, desmoplastic fibromas, Ewing's sarcomas, fibrous dysplasias, nonossifying fibromas, and malignant hemangioenkdotheliomas of bone. In order to elucidate the role of macrophages and osteoclast-like giant cells, different monoclonal antibodies were applied to bone tumor specimens as markers of mononuclear macrophages and giant cells. The concept of what is called fibrohistiocytic tumors should be reconsidered. Immunohistological studies have shown that in malignant fibrous histiocytoma as well as in giant cell tumors of bone only a certain portion of macrophages will react with the highly specific antibodies, whereas the majority of tumor cells are negative. This finding alone suggests that the infiltration of macrophages is a reactive phenomenon. It is in agreement with earlier autoradiographic and electron microscopic investigations on giant cell tumors of bone, confirming that only the fibroblast-like tumors are actually proliferating. These data were verified in the present study with the aid of double labeling immunohistological techniques, using antibodies against mature tissue macrophages and others against a proliferation-associated nuclear antigen. Only the fibroblast-like cells, which do not react with the macrophage-specific antibody, will express the proliferation-associated nuclear antigen. Analogous results were obtained in malignant fibrous histiocytoma. We may infer from these results that the majority of these tumors must be neoplasms of local mesenchyme, mostly in fibroblastic differentiation, while the considerable number of macrophages is seen as a reactive phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Neoplasms↗

Metastatic human melanoma. Phenotypic heterogeneity and antigen expression in relation to the clinical status.

According to animal experiments, metastasis to a particular organ depends on the phenotype of the tumor cells. Widespread metastatic dissemination including internal organs would therefore, at least in part, depend on the capacity of tumor cells to modulate, resulting in increased phenotypic heterogeneity. We found evidence for this assumption in human melanoma by phenotyping metastases (mainly cutaneous/subcutaneous) from 59 patients by the use of six monoclonal antibodies. Interlesional antigenic heterogeneity was present in 22/33 (67%) patients with disseminated metastases including at least one internal organ, but only in 4/26 (15%) patients whose metastases were restricted to skin and/or skin-draining lymph nodes (P less than or equal to 0.01). Chemotherapy cannot be the main reason for interlesional phenotypic heterogeneity, as seen by comparison of treated and untreated patients. Aneuploid melanoma metastases, as an indication for instability on the chromosomal level, were found in the majority of patients (84%) regardless of their clinical situation. Widespread disease was significantly related to the loss of the cytoplasmatic antigen K-1-2 and to the expression of the 130-kDa membrane antigen A-1-43.

Antigens, Neoplasm↗

Electroelution of antigens immobilized on antibody-linked affinity matrices.

An electrophoretic elution procedure for desorption of antigens from antibody-linked gel matrices is described which is performed in a commercially available elution device. The technique presented does not involve denaturing conditions such as chaotropic reagents or low and high pH elution buffers. Comparison of electroelution and conventional elution with acidic buffer reveals that the techniques is especially suitable for monoclonal antibodies with high affinity for their ligands. Recovery of antigens after electroelution is significantly higher than by desorption with glycine-HCl, pH 2.5. There is no loss of antigens during post-elution procedures. Proteins are obtained in small elution volumes and can be desalted without sample transfer.

Angiogenesis Inducing Agents↗

Immunohistochemical demonstration of migration inhibitory factor in different types of urticaria.

Because urticarial lesions can persist for extended periods of time, we have investigated the histochemical expression of an antibody against the cytokine macrophage inhibitory factor in 23 patients with different types of urticaria. Positive staining of upper and middermal dendritic cells was noted in sections from all three biopsy specimens of acute urticaria, eight of chronic urticaria, and all six of urticaria pigmentosa lesions. In all but one biopsy specimen, endothelial cells reacted as well. In three sections (two chronic urticaria, one urticaria pigmentosa), luminal lining cells of sweat glands were also noted to stain positively. In contrast, lesional skin from all eight patients with pressure urticaria was negative, as was the clinically normal skin of all patients, with the exception of one patient with urticaria pigmentosa. The data suggest that cytokines may be involved in lesions of acute type immunologic processes and that they need not be expressed in delayed type reactions.

Acute Disease↗