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Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

At least 181 records · Page 10Linked to original sources
PubMed1992

Infiltrating neutrophils differ from circulating neutrophils when stimulated with C5a, NAP-1/IL-8, LTB4 and FMLP.

In this study we report on functional characteristics of pustule as well as blood polymorphonuclear neutrophils (PMN) in a patient suffering from relapsing bullous staphyloderma. Large numbers of viable PMN from newly formed pustules as well as from the peripheral blood were investigated. During the course of disease chemotactic migration, enzyme degranulation, superoxide-anion generation and leukotriene B4 production were determined simultaneously. The results revealed C5a- and NAP-1/IL-8-specific dysfunction of pustule PMN as compared with blood PMN. In contrast, FMLP-elicited functional activities of pustule PMN were only slightly affected. Our findings provide evidence that in inflamed tissue invading PMN are regulated by in situ generated mediators. C5a produced by staph, aureus-induced activation of the alternative pathway of the complement cascade represents a predominant regulatory factor in situ. Furthermore, the results substantiate previous observations concerning different modulation of C5a and f-met-peptide receptors on human PMN.

Chemotaxis, Leukocyte↗
PubMed1992

Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality.

The adult respiratory distress syndrome (ARDS) is characterized by increased neutrophils within the airspaces of the lungs. In order to determine if neutrophil activating protein (NAP)-1/interleukin-8 (NAP-1/IL-8) could be an important cause of neutrophil influx and activation in ARDS, we examined fluid, which was either directly aspirated or lavaged with saline from the lungs of patients with ARDS. NAP-1/IL-8 was present in significantly higher concentrations in the fluids of patients with ARDS compared with control subjects. There was a significant correlation between the percentage of neutrophils in the lavage fluids and the NAP-1/IL-8 concentration (r2 = 0.74). Furthermore, the NAP-1/IL-8 concentration of the pulmonary edema fluid was equivalent to the optimal concentration required to induce neutrophil chemotaxis in vitro. Although not all of the chemotactic activity of the edema fluid was removed by an anti-NAP-1/IL-8 affinity column, the data established that NAP-1/IL-8 is an important neutrophil chemotaxin in the airspaces of patients with ARDS. In addition, those patients with very high concentrations of NAP-1/IL-8 in their bronchoalveolar lavage fluids had a higher mortality rate than those patients with lower concentrations of NAP-1/IL-8. The correlation between NAP-1/IL-8 concentration and mortality is not paralleled by total protein concentration and mortality.

Adolescent↗
PubMed1992

Candida albicans grown in glucose-free media contains serum-independent chemotactic activity.

Infection of skin with Candida albicans is usually followed by infiltration of neutrophil granulocytes (PMN). So far, chemotaxins for PMN have been isolated from C. albicans cultures grown in the presence of glucose. However, since glucose is not present in skin in vivo, a contribution of such factors to Candida-triggered cutaneous inflammation would appear unlikely. In order to clarify this question, chemotactic activity was measured in extracts from three different strains of C. albicans which were grown in five different peptone media free of carbohydrates and serum. In addition, four culture systems were supplemented with lipids normally present in human stratum corneum, including a triglyceride, cholesterol, and sphingomyelin. In all sugar-free grown cultures, serum-independent chemotactic activity was detected by use of the Boyden chamber technique. Since, as shown here in vitro, production of neutrophil chemotaxins by C. albicans is independent of glucose-feeding, a possible role of Candida-chemotaxins in the pathophysiology of cutaneous candidosis can no longer be excluded.

Candida albicans↗
PubMed1992

Relapsing bullous staphyloderma.

Relapsing eruptions of bullae rapidly turning into pustules were seen in a 69-year-old woman of good general health. At different times during several months of observation, strains of S. aureus were grown from various lesions, including one (phage group III) producing enterotoxin C. Systemic involvement except for high BSR was absent and repeated blood cultures were negative. Histopathological findings resembled impetigo. Antibiotic treatment was effective. As this disease does not fit into any of the well-known pustular infectious dermatoses, we suggest calling it relapsing bullous staphyloderma.

Aged↗
PubMed1991

Neutrophil-activating peptide 1/interleukin 8 mRNA expression and protein secretion by human monocytes: effect of cyclosporin A.

Neutrophil-activating peptide 1/interleukin 8 (NAP-1/IL-8) is a recently described cytokine with potent chemotactic activity for human neutrophil granulocytes (PMN) and T cells. In psoriasis, a chronic hyperproliferative and inflammatory skin disorder, PMN and T cells are found as prominent cells in the inflammatory infiltrate of the lesions; however, monocytes were shown to be the first cells invading a newly formed plaque. NAP-1/IL-8 was found to be present in high amounts in the skin and in scale material of psoriatic patients. Psoriasis responds well to systemic treatment with cyclosporin A (CsA), an immunosuppressive peptide. Therefore, we addressed the question of whether the clinical improvement of psoriatic patients during CsA therapy may be due to an inhibition of NAP-1/IL-8 production and secretion from monocytes. Purified human monocytes were stimulated by lipopolysaccharide in the presence or absence of various concentrations of CsA. Production of NAP-1/IL-8 was determined as expression of specific mRNA by fluorescent in situ hybridization. Secreted peptide was measured by bioassay (PMN chemotaxis) and enzyme-linked immunosorbent assay (ELISA) using specific monoclonal antibodies. The results show that CsA neither inhibited mRNA expression for NAP-1/IL-8 nor secretion of the peptide. These findings support the hypothesis that the pharmacological effect of CsA may be restricted to the inhibition of T-cell activation and proliferation.

Cyclosporins↗
PubMed1991

Inflammatory properties of neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8) in human skin: a light- and electronmicroscopic study.

Neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, was injected intracutaneously into human skin. Sequential biopsy specimens were taken in order to investigate the sequence of ultrastructural changes induced by the cytokine. Whereas intracutaneous injection of 100 ng of NAP-1/IL-8 per site caused no macroscopic changes, by histology infiltration with polymorphonuclear leukocytes (PMN) and monocytes was present within 1 h and increased at 3 and 5 h. No lymphocyte infiltration was noted. The first ultrastructural changes (30 min) consisted of the presence of cytoplasmic 7-nm microfilament bundles, as well as numerous protrusions of the luminal plasma membrane of endothelial cells (EC). As a striking feature, multiple 100- to 160-nm electron lucent vesicles could be observed in the EC cytoplasm. These structures differed from plasmalemmal vesicles and suggest secretory activity. When PMN and monocytes appeared in the vascular lumen (1 h and later), the number of 100-160-nm electron-lucent vesicles had decreased significantly. In contrast to C5a-injected skin sites, mast cell degranulation was absent.

Complement C5a↗
PubMed1991

Metabolism of arachidonic acid by human epidermal cells depends upon maturational stage.

Synthesis of 12- and/or 15-HETE by human epidermal cells was investigated after separating basal cells from suprabasal epidermal cell layers. We found that the main metabolite of 3H-arachidonic acid (3H-AA), formed by freshly prepared upper epidermal layers (stratum granulosum and spinosum), upon RP-HPLC co-eluted with authentic 3H-12-HETE. A 3H-15-HETE co-eluting peak selectively occurred in chromatograms obtained from supernatants of fractions containing basal cells. Supernatants of freshly prepared suspensions rich in basal keratinocytes appeared to contain 3H-15-HETE as their main 3H-AA metabolite, by far exceeding the recovered amounts of 3H-12-HETE. Moreover, keratinocytes cultured for 1 week or longer were found to produce predominantly a 3H-AA metabolite co-eluting with 3H-15-HETE. In supernatants of cultured cells, little if any 3H-12-HETE was detectable. Cultured human skin fibroblasts were not found to produce relevant amounts of HETE. Genuine tissue rich in basal cells, i.e., cells of hair follicles, were found to form twice as much 3H-15-HETE as 3H-12-HETE (3H-15-HETE/3H-12-HETE-ratio = 1.9 +/- 0.8; n = 7). Apparently, different epidermal layers are able to produce a characteristic pattern of 3H-AA metabolites. 3H-15-HETE generation seems to be a marker for proliferating keratinocytes, whereas 3H-12-HETE formation appears to be typical for differentiating suprabasal epidermal cells. Our results may explain the heretofore varying patterns of AA-metabolites by keratinocytes reported in the literature.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1991

Type I and type II psoriasis show a similar usage of T-cell receptor variable regions.

In nonpustular psoriasis, principally two forms can be distinguished [Christophers E. Henseler T: Patient subgroups and the inflammatory pattern in psoriasis. Acta Dermatol Venereol 69(suppl 151):88-92, 1989): Type I frequently shows positive family history, linkage disequilibrium for human leucocyte antigens (HLAs) Cw6, B13 and Bw57 as well as an early onset. Type II manifests itself around the 5th decade, it is more frequently than normal associated with Cw2 and B27. In the light of this association with HLAs an autoimmune pathogenesis has been discussed. In order to investigate the pathogenetic function of T cells we obtained biopsies from patients with type I (n = 10) and type II (n = 10) psoriasis. Three-step peroxidase staining was performed using a panel of monoclonal antibodies directed against five variable (V) regions of the beta chain (V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12) and one of the alpha chain (V alpha 2) of the T cell receptor (TCR). Positive or negative selection of a particular TCR V region could not be detected in the demonstrable repertoire. Furthermore, the usage of the V regions under investigation revealed a similar pattern in the two forms of psoriasis.

Adult↗
PubMed1991

Localization of neutrophil-activating peptide-1/interleukin-8-immunoreactivity in normal and psoriatic skin.

Various cytokines have in the past been detected in human skin. Among these, the neutrophil-activating peptide NAP-1/IL-8 is a potent 8-kD proinflammatory peptide that has been purified from psoriatic scales. Its chemotactic activity on human neutrophils, as well as its presence in psoriatic scales, may relate to a role in this disease. In the present study, the tissue distribution of the peptide was examined immunohistochemically using two monoclonal antibodies (52E8, 46E5) recently produced and characterized in our laboratory. Immunoreactivity was detected in both normal and psoriatic skin, resulting in uniform suprabasal keratinocyte staining in normal skin with 52E8 and of all keratinocytes with 46E5. Immunoreactivity in psoriasis correlated to the inflammatory tissue reaction, varying from uniform absence in highly active psoriasis to focally weak staining in plaque type psoriasis. Cells of the acrosyringium and hair follicles were always positive and were unaffected by the inflammatory activity. Epidermal immunoreactivity detected in this study may be associated with closely related peptides of the IL8 family or with truncated or extended forms of NAP-1/IL-8.

Antibodies, Monoclonal↗
PubMed1991

[The enzyme release by Trichophyton rubrum is dependent on nutritional substance supply].

Enzymes liberated by growing dermatophytes are of pathogenetic importance in tinea. To investigate the influence of nutrients on this enzyme release, Trichophyton rubrum was grown in media containing peptone, keratin and lipids, to which glucose was added in separate assays. The culture supernatants were compared for extracellular enzyme activities by use of the api-zym-test. Our results clearly show that the extracellular enzyme activity is dependent on the nutrients supplied. Seven different enzymes were released when keratin was supplied, as compared to only 5 and 2, respectively, when lipids or peptone were available. Among these enzymes alkaline phosphatase and N-acetyl-beta-glucosaminidase were detected in all cultures lacking glucose. Enzyme release was inhibited completely when glucose was added to the media, except for N-acetyl-beta-glucosaminidase in peptone cultures. This dependency of enzyme release on fungal nutrition can be expected to occur in vivo, too. In addition, it has to be considered for in vitro cultural conditions. Alkaline phosphatase and acetyl-glucosaminidase may be more important in tinea than has been assumed so far.

Culture Media↗
PubMed1991

[Cryofibrinogenemia--successful therapy by decreasing fibrinogen].

Six patients suffering from solitary cryofibrinogenaemia are described. In one patient idiopathic cryofibrinogenaemia was present, while the others showed secondary cryofibrinogenaemia associated with borrelia infection, chronic venous insufficiency with pulmonary embolism, primary biliary cirrhosis, diabetes mellitus or von-Willebrand syndrome. Subcutaneous injections of the thrombin-like snake poison batroxobin/ancrod were administered over a period of several weeks. Five patients experienced almost complete remission of their symptoms, especially of pain following cold exposure. In one patient partial relief was achieved. Overall we found a 75% reduction of symptoms. When blood fibrinogen levels are carefully monitored this therapy is an efficient and safe form of treatment for cryofibrinogenaemia.

Adolescent↗
PubMed1990

Identification of a novel platelet-derived neutrophil-chemotactic polypeptide with structural homology to platelet-factor 4.

A novel protein, NAP-4, could be isolated from human platelet lysates. NAP-4 preparations induced chemotaxis of human neutrophils with an ED50 near 400 ng/ml. Purification by anti NAP-1/IL-8 affinity chromatography and reversed phase HPLC revealed a single peak showing a single line upon SDS-PAGE corresponding to a Mr of 8000. NH2-terminal sequence analysis indicated an unique sequence showing strong homology to human platelet factor 4 and weak homology to tumor necrosis factor alpha as well. The most interesting finding is the absence of the first two cysteins, known to be strongly conserved in members of the family of platelet-factor 4-like host defense cytokines.

Amino Acid Sequence↗