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Biomedical subjects

A Kapp

Publications and source records attributed to A Kapp.

At least 235 records · Page 13Linked to original sources
PubMed1986

Granulocyte-activating mediators (GRAM): I. Generation by lipopolysaccharide-stimulated mononuclear cells.

We undertook a study to determine whether cytokines exist which are responsible for the activation of polymorphonuclear neutrophilic granulocytes (PMN) besides the already well-known stimuli. Lucigenin-dependent chemiluminescence was used to measure human PMN activation. Addition of supernatants from mononuclear cells stimulated with bacterial lipopolysaccharide produced a long-lasting activation of granulocytes. Induction of chemiluminescence was dose-dependent and inhibitable by superoxide dismutase. Fractionation of mononuclear cells by adherence to plastic dishes or counterflow elutriation proved that monocytes were able to generate granulocyte-activating mediators (GRAM). Production of GRAM was dependent on the dose of the stimulus and appeared to be maximal after 24 h of incubation. Addition of cycloheximide resulted in significantly decreased release of GRAM. Partial characterization of the activity showed GRAM to be heat-labile and sensitive to trypsin, indicating a protein nature of GRAM. The activity fractionated into 2 distinct peaks, one corresponding to 60 kD and another below 10 kD. The interleukin 1 activity did not appear to co-fractionate with GRAM. Evidence presented suggests that the activity corresponds to factors unlikely to have been described previously.

Chemotactic Factors↗
PubMed1986

Detection of circulating immune complexes in patients with atopic dermatitis and psoriasis.

Sera from 32 patients with atopic dermatitis and 22 patients with psoriasis were examined for the presence of circulating immune complexes (CIC) in comparison to 51 healthy controls using a PEG-precipitation laser nephelometer technique. Different patterns of the precipitated proteins were found in both diseases. In atopic dermatitis C3 and IgG were significantly elevated in CIC. Furthermore, significantly increased amounts of IgE were found in the precipitates. Groups with high and low serum IgE levels showed no significant differences in the quantity of precipitated proteins. Skin involvement did not correlate with CIC. In psoriasis patients, a different pattern with significantly increased IgA, IgG, IgM and C3 was found in the precipitates. IgE was also significantly increased in comparison to the controls. No difference was found between patients with psoriasis vulgaris and psoriasis guttata. CIC in psoriasis and in atopic dermatitis thus showed a characteristic composition. However, a detection of CIC was not directly related to the cutaneous manifestation of the disease.

Antigen-Antibody Complex↗
PubMed1986

Cellular reactivity of polymorphonuclear leukocytes in psoriasis and atopic dermatitis--measurement of lucigenin-dependent chemiluminescence.

Polymorphonuclear leukocytes (PMN) of patients suffering from psoriasis and atopic dermatitis are supposed to differ in their function from the PMN of normals. However, conflicting results have been reported. Using a lucigenin-dependent chemiluminescence we investigated the response of isolated PMN from patients with atopic dermatitis (AD) and psoriasis to different stimuli. PMN of 17 patients with psoriasis and 13 patients with AD with mild to moderate disease activity were stimulated with a chemotactic peptide (f-met-phe), zymosan activated serum (ZAS), zymosan particles and phorbol myristate acetate. In the AD group we found a significantly decreased response after stimulation with ZAS in comparison to the controls. With the other stimuli tested no significant difference was detected. In comparison to normal controls psoriatic PMN showed no significant difference with any of the stimuli. Comparing patients with plaque-type and guttate-type psoriasis no significant difference was detected. We suggest that the reported hyperactivation of psoriatic PMN could be triggered by serum factors which were excluded in the present investigation. The decreased response of PMN to stimulation with ZAS from patients with AD associated with a normal reactivity to the other stimuli could be due to specific desensitization of the PMN by C5a in vivo.

Acridines↗
PubMed1986

Novel neutrophil chemotactic factor derived from human peripheral blood mononuclear leucocytes.

Human mononuclear leucocytes isolated from the peripheral blood by centrifugation on Ficoll-Hypaque cushions and adherent on plastic petri dishes, produced a chemotactic factor that attracted human neutrophilic granulocytes to the same extent as did optimal concentrations of the complement split product C5a and the leukotriene B4. The active component eluted from a Sephadex G-50 gel filtration column as a single peak with an apparent molecular weight of 10,000. The chemotactic activity was resistant to reductive cleavage of disulfide bonds and heating at 100 degrees C for 30 min but was lost when reduction and heating were combined. Digestion with a proteolytic enzyme eliminated the attractive potential. The data suggest that this is a novel chemotactic peptide. It is conceivable that it has been seen previously and was mistaken for a lymphokine or interleukin 1.

Chemotactic Factors↗
PubMed1986

Induction of granulocyte chemiluminescence by a mediator derived from human monocytes.

Neutrophil granulocytes are most active producers of potentially toxic free oxygen radicals. Since other functions of granulocytes can be affected by lymphokines or monokines, we investigated whether granulocyte oxygenation activity can also be influenced by such cellular mediators. Human granulocytes emitted strong chemiluminescence after addition of culture supernatants from human mononuclear cells stimulated with bacterial lipopolysaccharide (LPS). Response of the granulocytes was dose-dependent and was inhibited up to 90% or more by superoxide dismutase. This granulocyte chemiluminescence inducer-activity (GCI-activity) in the LPS-induced supernatants was heat-labile and sensitive to trypsin treatment. Addition of cycloheximide to the cultures inhibited the generation of GCI-activity by 80%. On HPLC gel filtration GCI-activity eluted with two distinct peaks corresponding to molecular weights of 60 +/- 10 KDa and between 1 and 5 KDa. Murine interleukin 1, human recombinant interferon-alpha and -gamma were devoid of GCI-activity. When mononuclear cells were fractionated by plastic adherence or counterflow elutriation, monocytes appeared to be the source of GCI-activity. Therefore, it appears that granulocyte oxygenation activity can be enhanced strongly by a cellular mediator derived from monocytes. This interaction of monocytes and granulocytes may constitute a new and potent pathway of phagocyte-dependent production of highly reactive and potentially toxic oxygen radicals.

Cell Adhesion↗
PubMed1985

Detection of complement activation in human serum using C5a-induced chemiluminescence of human granulocytes.

The complement system can be activated by many factors, including immune complexes, leading to the generation of biologically active split products like C5a anaphylatoxin. This study presents a technique which may be used for measuring C5a activity in human serum. The tetanus-anti-tetanus immune complex and aggregated human IgG were used as model activators of the complement cascade. The C5a activity was measured by C5a-induced chemiluminescence of granulocytes; furthermore, a radioimmunoassay was used to detect the C5a peptide. There was a strongly positive correlation between the two assay systems. The described method should be useful as an alternative means of detecting complement activation in the serum of patients with inflammatory diseases.

Antigen-Antibody Complex↗
PubMed1985

Involvement of complement in psoriasis and atopic dermatitis--measurement of C3a and C5a, C3, C4 and C1 inactivator.

Normal complement components and activation products were determined in the peripheral blood of 35 patients with atopic dermatitis (AD) and 24 patients with psoriasis at a mild to intermediate stage. None of the patients had received systemic or local steroid therapy 6 weeks prior to blood collection. Levels of C3, C4 and C1 inactivator (C1 INA) were determined in serum by radial immunodiffusion, whereas C3a and C5a levels were measured by radioimmunoassay. In comparison to healthy non-atopic controls, the levels of C3, C4 and C1 INA were found to be significantly increased in both diseases. No substantial differences were detected between patients with psoriasis vulgaris and psoriasis guttata, which suggests that the dissimilarities found were not due to preceding or concomitant infections. In AD, there was a tendency towards increased C3a levels, whereas in psoriasis, C3a levels were significantly increased. In both diseases, no measurable amounts of C5a could be detected. The results indicate that, in both AD and psoriasis, the complement participates in the inflammatory process. Elevated levels of C3a suggest that there is a continuous activation of the complement system leading to the generation of inflammatory mediators.

Adolescent↗
PubMed1985

Diverticular abscess of colon: irritative bladder symptoms.

Diverticular disease can affect the bladder in subtle ways. Presented herein is a case of a chronic abscess secondary to diverticulitis presenting as irritable vesical symptoms overlooked for several years. The value of pelvic computerized tomography in the diagnosis is stressed.

Abscess↗
PubMed1985

Involvement of complement in atopic dermatitis.

There is little information about the role of complement in atopic dermatitis (AD). We studied the levels of both normal complement components and activation products in peripheral blood of patients with mild to intermediate disease. 35 patients had not received systemic or topical steroid therapy 6 weeks prior to blood collection. C3, C4 and C1 INA were determined in serum by radioimmunodiffusion. C3a and C5a levels were measured in EDTA plasma by radioimmunoassay. Compared to healthy non-atopic controls C3, C4 and C1 INA were found to be increased significantly. There was a tendency towards increased C3a levels but the difference was not significant. No measurable amounts of C5a were detected. Elevations of C3a were correlated with elevated levels of C3. The results suggest that the complement system participates in the inflammatory process in AD.

Adolescent↗
PubMed1985

[Pathogenesis of atopic dermatitis].

Atopic dermatitis (AD) is a familial inflammatory skin disorder which is characterized by extreme pruritus, the typical morphology and distribution, the chronic or chronically relapsing time course and the personal or family history of atopy (asthma, allergic rhinitis, atopic dermatitis). However, there exists a variety of additional features which are either less specific or relatively rare. Although this disease has been well-known since the beginning of the century, the pathogenesis is not clearly understood at present. This review summarizes the reported deviations of the immune system as well as the alterations of the mediators of inflammation and the abnormalities of cyclic nucleotide regulation. These findings will be correlated with clinical symptoms. In particular the following topics were taken into consideration: association with HLA-antigens, elevation of serum IgE and generation of IgE immune complexes, numerical and functional deficiencies of T-suppressor cells, involvement of granulocytes, alterations of mediators of inflammation and especially the observations on the cyclic adenosine monophosphate (cAMP)-phosphodiesterase. These extremely complex findings based on the interaction between disregulation of the autonomous nervous system and alterations of the immune system may provide a better understanding of the pathogenesis of atopic dermatitis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

C5a-induced chemiluminescence of human granulocytes and its amplification by a serum factor.

Purified human C5a elicits a fast chemiluminescence (CL) response from isolated human granulocytes in the presence of Lucigenin (bis-N-methylacridinium nitrate). The reaction is inhibitable to more than 90% by superoxide dismutase (SOD) - final concentration 200 micrograms/ml -, to about 60% by catalase - final concentration 10 mg/ml - and to 30% by the hydroxyl radical scavenger D-mannit - final concentration 100 mM. Therefore O2- seems to be the oxygen radical responsible for most of the CL, while OH and H2O2 are also involved. Addition of normal pool serum to the cells for 1-2 min before stimulation with C5a strongly enhances the effect in a dose and time-dependent manner. Therefore the existence of a "helper activity" in serum amplifying the C5a-induced CL of granulocytes is postulated. This "helper activity" is, however, no specific for C5a, since CL responses elicited with the chemotactic peptide f-met-phe or by phorbol-myristate-acetate (PMA) are also enhanced by preincubation with serum. In contrast, ConA-induced CL is not enhanced but decreased. Therefore, though not unique to C5a-induced CL, the "helper activity" seems not to represent a general "adjuvans" effect of serum on the granulocytes, but to be restricted to certain stimuli.

Chemotaxis, Leukocyte↗
PubMed1978

T-cell function in atopic dermatitis. Controlled examination of concanavalin A dose-response relations in cultured lymphocytes.

The Concanavalin A (Con A) stimulation response of peripheral lymphocytes in vitro was found to be decreased statistically significant (alpha = 0.005) in patients with light atopic dermatitis, Strictly matched pairs were examined. Using ten graded concentrations of Con A, dose-response relations of the pairs were demonstrated, differences were more evident at lower suboptimal concentrations. Background DNA-synthesis of the patients was elevated.

Cells, Cultured↗
PubMedDate not supplied

The CC chemokine receptor antagonist met-RANTES inhibits eosinophil effector functions.

Eosinophils play an important role in allergic diseases such as allergic asthma, rhinoconjunctivitis and atopic dermatitis. Recruitement of eosinophils to the side of inflammation, the release of reactive oxygen species, leading to tissue damage, and the propagation of the inflammatory response are mediated by chemokines. Thus, the applicability of agents able to inhibit or antagonize chemokine-induced eosinophil activation seems to be of interest in the treatment of allergic diseases. Therefore, the effect of the CC chemokine antagonist, Met-RANTES, on its effect on human eosinophil effector functions in response to RANTES, MCP-3 and eotaxin was investigated. Met-RANTES had no intrinsic activity on [Ca2+]i transients in eosinophils and was able to dose-dependently inhibit [Ca2+]i transients in eosinophils following stimulation with RANTES, MCP-3 and eotaxin. Besides its effect on [Ca2+]i transients, Met-RANTES dose-dependently inhibited actin polymerization in eosinophils and the release of reactive oxygen species following stimulation with RANTES, MCP-3 and eotaxin. The results of this study lead to the conclusion that Met-RANTES is an effective and powerful compound to antagonize effector functions of human eosinophils following stimulation with RANTES, MCP-3 and eotaxin and is therefore a promising therapeutic approach to prevent the invasion and destructive power of eosinophils in allergic diseases.

Calcium↗
PubMedDate not supplied

Aminooxypentane-RANTES induces CCR3 activation and internalization of CCR3 from the surface of human eosinophils.

Eosinophils are predominant effector cells in allergic diseases attracted by several CC chemokines into the inflammatory tissue. According to their important role in attracting leukocytes, several kinds of chemokine receptor antagonists have been developed. Therefore, the aim of this study was to investigate the effect of aminooxypentane (AOP)-RANTES on the activation of the CC chemokine receptor 3, CCR3, exemplary on human eosinophils, because they represent the dominant CCR3+ cell type. AOP-RANTES dose-dependently induced an increase of intracellular calcium concentration ([Ca(2+)](i)) and a release of reactive oxygen species, which could be inhibited by pertussis toxin, in human eosinophils from normal nonatopic donors. AOP-RANTES was as effective as RANTES but less effective than eotaxin and eotaxin-2 in the activation of the respiratory burst. Flow-cytometric analyses revealed that eosinophils constitutively expressed the CC chemokine receptors CCR1 and CCR3, whereas CCR5 was not expressed. AOP-RANTES, RANTES, eotaxin and eotaxin-2, but not Met-RANTES, induced a downregulation of CCR3 at 37 degrees C. Reexpression of CCR3 on eosinophils was observed within 120 min. Whereas no differences of CCR3 downregulation and recycling after stimulation with AOP-RANTES, RANTES, eotaxin and eotaxin-2 were found there exists a distinct profile of activity with respect to the activation of the respiratory burst in human eosinophils.

Cells, Cultured↗