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C Sunderkötter

Publications and source records attributed to C Sunderkötter.

At least 19 recordsLinked to original sources
PubMed1996

E-selectin expression in experimental models of inflammation in mice.

E-selectin (CD62E, formerly termed ELAM-1) is a cytokine-inducible adhesion molecule which mediates the binding of neutrophils, monocytes, and skin homing T-cells. The murine homologue of E-selectin has been cloned. A monoclonal antibody (21KC10) was used here to study immunohistochemically the expression and regulation of murine E-selectin in vitro and in vivo. As described for the human system, there was no staining of normal endothelium in skin and other tissues. LPS and tumour necrosis factor-alpha (TNF-alpha), but not interleukin-4 (IL-4) or interferon-gamma (IFN-gamma), induced a transient expression of E-selectin, both when injected in vivo and when added to endothelial cell lines in vitro. To analyse temporal expression of E-selectin under pathophysiological conditions in vivo, we chose two murine models of inflammation: allergic (ACD) and irritant contact dermatitis (ICD). Expression of E-selectin was found to be induced on vascular endothelium of post-capillary venules in both ACD and ICD. In ICD, maximal staining of endothelial cells occurred earlier than in ACD. Expression of E-selectin during ICD and ACD was then compared between strains of mice which differ with regard to the intensity of their inflammatory reaction. BALB/c mice, which in contrast to C57BI/6 mice show a denser infiltrate and prolonged influx of granulocyte and monocytes, revealed a more pronounced and more prolonged expression of E-selectin than C57BI/6 mice. This held true for both ACD and ICD, and in each case, peak expression of E-selectin was associated with the highest density of the leukocytic infiltrate. This study thus reveals regulatory mechanisms involved in the expression of murine E-selectin in vivo and in vitro. It also demonstrates a correlation between endothelial expression of E-selectin and the genetically determined intensity of the inflammatory response.

Animals↗
PubMed1996

Activated T cells induce expression of E-selectin in vitro and in an antigen-dependent manner in vivo.

E-selectin is an endothelial adhesion molecule for polymorphonuclear cells, monocytes and skin-homing T cells. We have analyzed whether murine T cells are able to induce expression of E-selectin in vitro and in vivo. Using models of inflammation in which T cells play either a significant or only a minor role, we compared induction of E-selectin between normal mice and mice lacking functional T cells (athymic nude mice). In irritant contact dermatitis, a model without a major role for T cells, E-selectin was transiently expressed within the first 24 h in both normal and nude mice. In experimental leishmaniasis (where specific T cells play an important role), a high expression of E-selectin was maintained for 48 h in normal mice, whereas in nude mice expression was only transient. However, reconstitution of nude mice with 10(8) T cells from draining lymph nodes (LN) of Leishmania-infected normal mice could restore sustained expression of E-selectin. Transfer of T lymphocytes from normal LN or from LN of mice sensitized to the contact allergen trinitrochlorobenzene (TNCB) did not have this effect. T cells from TNCB-sensitized mice, however, did induce sustained expression of E-selectin in nude mice when TNCB was applied locally; here, reconstitution with Leishmania-specific T cells had no effect. In vitro, T cells from infected or TNCB-sensitized normal mice increased expression of E-selectin on microvascular endothelial cells after 4 h of co-culture. T cells from untreated mice were less effective. Induction was dependent on direct cell-cell contact, but not on the action of interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha or interferon-gamma. We conclude that sensitized T cells induce sustained expression of E-selectin in vivo in an antigen-dependent manner. This novel way of regulation could be relevant for cell-mediated immunity and chronic disease. The mechanisms are unknown, but, as in vitro, might require direct cell-cell contact.

Animals↗
PubMed1995

[Life threatening angioedema caused by acquired C1 inhibitor deficiency associated with paraproteinemia and livedo racemosa].

A 61-year-old patient with life-threatening angioneurotic oedema was found to have an acquired C1-inhibitor (C1-INH) deficiency. In addition to lowered serum levels of C1-INH (both protein concentration and enzymatic activity), C2, C4 and CH50, which are characteristic for the hereditary form of angioneurotic oedema, markedly lowered C1q was found, which is typical for the acquired form. There were no antibodies against C1-INH. Repeated thorough examination disclosed no neoplasm, though the presence of neoplasm has often been reported to be associated with the acquired C1-INH deficiency. However, the patient showed persistent paraproteinaemia and paraproteinuria and developed livedo reticularis. Treatment with danazol resulted in a rise of the complement fraction levels and cessation of angioneurotic oedema. Paraproteinaemia and livedo reticularis persisted unchanged.

Angioedema↗
PubMed1995

Successful treatment of epidermolysis bullosa acquisita using intravenous immunoglobulins.

We report a 55-year-old man with severe inflammatory epidermolysis bullosa acquisita. The skin lesions did not respond to various immunosuppressive treatments. The combined administration of prednisone, azathioprine, dapsone and colchicine resulted only in a transient and incomplete resolution of the lesions. The bullae and increased skin fragility were successfully controlled by the addition of high-dose intravenous immunoglobulin therapy.

Azathioprine↗
PubMed1995

Treatment of urticaria pigmentosa using interferon alpha.

Long-term treatment with interferon alpha (IFN-alpha) has recently been shown to reduce the bone marrow infiltrate and cutaneous lesions in systemic mast cell disease. We therefore administered this cytokine to six patients with urticaria pigmentosa for up to 12 months, using subcutaneous injections of 5 x 10(6) U, initially five times, and subsequently three times a week. The generally well-tolerated therapy resulted in marked improvement of the cutaneous symptoms, especially in three of the patients who suffered from very severe pruritus. Two of the patients with bone marrow infiltration showed normal findings after treatment. However, in none of the patients was there any change in the skin lesions, or decrease in the degree of cutaneous mast cell infiltration, as evidenced by light and electron microscopic examination. These findings indicate that IFN-alpha is highly effective in the control of symptoms, but otherwise does not influence the cutaneous lesions of urticaria pigmentosa.

Adult↗
PubMed1995

Chronic urticaria, arthralgia, raised erythrocyte sedimentation rate and IgG paraproteinaemia: a variant of Schnitzler's syndrome?

Schnitzler's syndrome is a distinct disease entity characterized by the association of chronic urticaria, intermittent fever, arthralgia, elevated erythrocyte sedimentation rate and IgM macroglobulinaemia. We report a patient with the same symptoms, but a monoclonal IgG instead of IgM gammopathy. Histological examination of the urticarial lesions showed signs of mild leucocytoclastic vasculitis. Except for the different class of the monoclonal immunoglobulin, the clinical symptoms, laboratory findings and histology in this patient were identical with those in classical Schnitzler's syndrome. IgG and IgM paraproteins may be equivalent with regard to the putative pathophysiology of the disease process in Schnitzler's syndrome. We therefore suggest that the spectrum of Schnitzler's syndrome is expanded to include patients with chronic urticaria and monoclonal IgG gammopathy, as a closely related variant.

Arthralgia↗
PubMed1994

Macrophages and angiogenesis.

Macrophages are supposed to play a key role in inflammatory and tumor angiogenesis. Their importance derives from (1) their ubiquitous presence in normal and especially inflamed tissues, (2) their potential to become activated in response to appropriate stimuli, and (3) their repertoire of secretory products. By release of proteases, growth factors (bFGF, GM-CSF, TGF-alpha, IGF-I, PDGF, VEGF/VPF, TGF-beta), and other monokines (IL-1, IL-6, IL-8, TNF-alpha, substance P, prostaglandins, interferons, thrombospondin 1), activated macrophages have the capability to influence each phase of the angiogenic process, such as alterations of the local extracellular matrix, induction of endothelial cells to migrate or proliferate, and inhibition of vascular growth with formation of differentiated capillaries. This review describes macrophage physiology and the influence of macrophage secretory products on the different phases of angiogenesis in vitro and in vivo.

Animals↗
PubMed1994

[Essential cryofibrinogenemia with generalized livedo racemosa].

A 45-year-old male patient presented with cold-induced generalized livedo reticularis, repeated acral ulcerations and purpura, Raynaud's phenomenon, and peripheral polyneuropathy. The patient also experienced malaise, vertigo, and transient amaurosis whenever he was exposed to low temperatures. Skin biopsies of the livedo reticularis revealed marked dilatation of the small dermal blood vessels and circumscribed leukocytoclastic vasculitis. Essential cryofibrinogenaemia was diagnosed on the basis of detection of this cryoprotein in the chilled blood plasma with increased viscosity. Pulsed therapy with dexamethasone and cyclophosphamide resulted in marked relief of the symptoms, and cryofibrinogen was no longer detectable in the patient's plasma.

Biopsy↗
PubMed1994

A unique non-Langerhans cell histiocytosis with some features of generalized eruptive histiocytoma.

A symmetric eruption of hundreds of coalescent small red macules and a few slightly elevated papules sparing the flexures was observed in a 73-year-old man. Light microscopic examination showed loose aggregates of small and large histiocytic cells. Electron microscopy showed an absence of Langerhans cell granules and lipid droplets. Features shared with generalized eruptive histiocytoma were the symmetry of the eruption sparing the flexures, the blue-red coloration, and the absence of lipid-containing foam cells and multinucleated giant cells. However, the primary occurrence of macules rather than papules or nodules, the tendency of the macules to coalesce, and the dimorphic histiocytoid infiltrate are not found in generalized eruptive histiocytoma. Nevertheless, immunohistochemistry confirmed that this unique condition is a form of MS-1+ cutaneous non-Langerhans cell histiocytosis.

Aged↗
PubMed1994

Expression of murine VCAM-1 in vitro and in different models of inflammation in vivo: correlation with immigration of monocytes.

VCAM-1 (vascular cell adhesion molecule-1) is a cytokine-inducible adhesion molecule which is known to mediate adhesion of mononuclear cells to endothelial cells in vitro via binding to the integrin VLA-4 (very late antigen-4). To further elucidate the role and regulation of VCAM-1 in vivo, we compared in vitro and in vivo expression of VCAM-1 in response to cytokines and investigated immunohistochemically the expression of VCAM-1 in three murine models of experimental inflammation. These models differed with regard to the pathogenetic mechanism and the subsequent infiltrate: allergic contact dermatitis (ACD) to DNFB as a T cell-controlled, DTH type of inflammation, cutaneous infection with Leishmania major as a chronic granulomatous inflammation and the cauterized cornea as a model for acute inflammation. VCAM-1 was found to be markedly enhanced on vascular endothelia in all types of inflammation and after subcutaneous administration of LPS and TNF-alpha. Administration of IL-4, however, failed to induce VCAM-1 both in vivo and in vitro. The increased VCAM-1 expression in the inflammatory models correlated with the appearance of infiltrating monocytes/macrophages. A concomitant influx of CD4-positive/CD8-positive lymphocytes was only observed in ACD and Leishmaniasis.

Animals↗
PubMed1993

Resistance of mice to experimental leishmaniasis is associated with more rapid appearance of mature macrophages in vitro and in vivo.

Resistance to murine leishmaniasis has been related to the propagation of specific Th cell subsets (Th1 and Th2). This study shows that there are differences between resistant and susceptible mice in the initial myelomonocytic infiltrate, which precede the specific T cell response. After subcutaneous injection of 2 x 10(7) Leishmania major into footpads of resistant C57Bl/6 and susceptible BALB/c mice we performed immunohistochemical studies on the infiltrate. Two days after infection the percentage of more mature, F4/80-positive macrophages in the lesion increased faster in C57Bl/6 mice (63%) than in BALB/c mice (29%). The same strain-specific differences were observed after infection of corresponding strains of athymic mice (57.2% in C57Bl/6 nu/nu; 33.6% in BALB/c nu/nu), thus excluding a T cell-controlled phenomenon. After 1 wk the infiltrate in susceptible mice began to reveal significantly more cells containing MRP14, which is expressed by granulocytes and less mature monocytes but not by mature macrophages. No corresponding differences were found between athymic strains, suggesting that at this point organization of the infiltrate falls under control of protective T cells. In bone marrow cultures of BALB/c and C57Bl/6 mice, the percentage of F4/80-positive macrophages was also increasing faster in C57Bl/6 mice than in BALB/c mice. Increased expression of the F4/80 Ag was associated with higher leishmanicidal activity of C57Bl/6 macrophages. MRP14-positive bone marrow cells on the other hand were rarely infected by parasites. We suggest 1) that the earlier appearance of leishmanicidal macrophages in lesions of C57Bl/6 mice could influence propagation of either Th1 or Th2 cells by reduction of parasite load or by differential secretion of decisive cytokines and 2) that the diffuse accumulation of granulocytes and inflammatory monocytes in susceptible mice facilitates spread of disease.

Animals↗
PubMed1993

Expression and complex assembly of calcium-binding proteins MRP8 and MRP14 during differentiation of murine myelomonocytic cells.

In the present study we analyzed expression and biochemical properties of the two recently cloned calcium-binding proteins MRP8 and MRP14, both members of the S-100 family, in murine myelomonocytic cells. Expression of MRPs was found to be restricted to granulocytes and distinct stages of macrophage differentiation when compared to the expression of other markers (Mac-1, F4/80) in transformed macrophage cell lines (M1, RMB.TG, WEHI.TG, J774A, P388D) and resident and exudate peritoneal and tissue macrophages. Similarly, mRNA and protein levels of MRP8/MRP14 in murine bone marrow cells decreased during culture in L cell-conditioned medium. Applying a cross-linking technique, the formation of noncovalently associated heteromeric MRP8/MRP14 complexes of 25, 35, and 48 kd was demonstrated. Our data suggest that MRP8/MRP14 expression and complexation are characteristic for granulocytes and distinct stages of macrophage differentiation in mice. Analysis of the MRP8/MRP14+ phenotype of macrophages may provide further insights into the mechanisms underlying macrophage differentiation.

Animals↗
PubMed1992

Expression of the calcium-binding proteins MRP8 and MRP14 by early infiltrating cells in experimental contact dermatitis.

The immune response to an allergen is not only dependent on the inflammatory stimulus, but also on the genetic disposition of the individual. Important effector cells in the immune response are myelomonocytic cells in their various differentiation stages. We recently described the expression of MRP8 and MRP14, two calcium-binding proteins of the S-100 family, by these cells during inflammatory activation. Here, we investigated whether their expression in murine contact dermatitis is dependent on the stimulus by which dermatitis is elicited, and if it is related to the genetic constitution of different inbred strains of mice. Therefore we performed immunohistochemical studies on the distribution of MRP8- and MRP14-positive cells during experimentally induced allergic (ACD) and irritant contact dermatitis (ICD). Both forms of dermatitis were elicited in BALB/c and C57B1/6 mice. BALB/c mice were found to react with a more intense inflammatory response in both ACD and ICD (high responders) than C57Bl/6 mice (low responders). The expression of MRP8 and MRP14 in both forms of dermatitis correlated with the early influx of macrophages and with the cell density of the infiltrate. Also the percentage of MRP8- and MRP14-positive cells in the infiltrate during ACD or ICD was higher in the more intense inflammatory reaction of BALB/c mice compared to C57Bl/6 mice. We conclude that MRP8 and MRP14 define a differentiation stage of inflammatory macrophages and that their expression correlates with the activity of inflammatory processes.

Animals↗
PubMed1991

Macrophage-derived angiogenesis factors.

A majority of angiogenic factors has been shown to be produced by macrophages. This review will give a concise description of their biochemical nature, their isolation from macrophages and their angiogenic activity. Among the factors with mitogenic effects on endothelial cells are basic fibroblast growth factor (bFGF), transforming growth factor-alpha (TGF-alpha) and very probably insulin-like growth factor-1 (IGF-1). Other secretory products such as angiotropin and human angiogenic factor (HAF) are nonmitogenic but promote angiogenesis by inducing migration of endothelial cells. Prostaglandins, platelet-derived growth factor (PDGF), granulocyte-macrophage- and granulocyte-colony stimulating factor (GM-CSF, G-CSF), interleukin 6 (IL-6) and angiotensin converting enzyme (ACE) have also been shown to be angiogenic, but their mode of action is still to be clearly defined. As the extracellular matrix appears to be involved in the control of angiogenesis, macrophage-derived factors that can alter this structure via degradation or via the clotting system will also be discussed. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1) and transforming growth factor-beta (TGF-beta) have complex actions on endothelial cells, and can partially inhibit angiogenesis. Among the factors which solely inhibit neovascularization are the interferons. As it is not known whether all of these factors play a role in angiogenesis in vivo attempts to detect them in situ during the course of neovascularization will be described. Finally macrophages will be discussed as cells that may not be mandatory for each phase of the angiogenic process but whose angiogenic capabilities are comprehensive and unsurpassed by any other cell.

Angiogenesis Inducing Agents↗
PubMed1991

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↗
PubMed1990

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↗