Distinct amplification of the C5a-receptor pathways in normodense and hypodense eosinophils of patients with atopic dermatitis.

In patients with atopic dermatitis two different types of blood eosinophils with distinct density can be isolated. The normodense cells represent the huge majority in count, whereas the hypodense eosinophils are characterized by higher effector activity. To understand the altered functional responsiveness of these two cell subtypes, the expression of C5a receptors as well as C5a-induced signal pathways and the production of reactive oxygen metabolites have been analyzed. Chemiluminescence measurements revealed significant higher production of reactive oxygen metabolites in hypodense eosinophils in comparison to normodense cells. However, no difference in the expression level of C5a receptors as well as in the C5a-induced Ca2+-transients between normodense and hypodense eosinophils were found. In contrast, hypodense eosinophils showed a significantly higher actin polymerization response and phosphatidylinositol 4,5 bisphosphate 3-kinase activation after stimulation with C5a than normodense eosinophils. Therefore, normodense and hypodense eosinophils from the blood of patients with atopic dermatitis are characterized by differential amplification of C5a-receptor signal pathways, which might explain the differences in their proinflammatory activity.

[Pregnancy in women with thyroid cancer treated with suppressive doses of L-thyroxine]. / Ciaza u kobiet z rakiem tarczycy leczonych supresyjna dawka L-tyroksyny.

UNLABELLED: The aim of the study was to estimate the dose of thyroxine required by pregnant women who had undergone total thyreoidectomy and radioiodine treatment for thyroid cancer. Material consisted of 4 pregnant women, aged mean 30.8 years. One of patients was studied during 2 consecutive pregnancies. The daily mean dose of thyroxine was 175 micrograms. The control group consisted of 7 women with primary hypothyroidism aged mean 33.5 years, who were treated with replacement doses of thyroxine. One of them was pregnant twice. The mean daily dose of thyroxine was 106.3 micrograms. The estimation of TSH, fT4 were repeated every 4 weeks. RESULTS: In all cases natural deliveries took place. All infants were alive and had no congenital malformations and no clinical or biochemical thyroid dysfunction was found. Pregnant women treated for thyroid cancer needed to have optimized their suppressive therapy by increasing the dose of thyroxine by 26% at the first trimester, 27% at the second and 38% at the last one. Statistically significant increase was found at the 1st trimester of pregnancy and it remained at the same level till the delivery. Pregnant hypothyroid women needed to have optimized their replacement thyroxine therapy by increasing of the dose by 53% at the first trimester, by 49% at the second and by 53% at the last one. Similarly to the 1st group of patients, we noticed statistically significant increase at the 1st trimester of pregnancy. CONCLUSION: In pregnant women who have been previously treated for thyroid cancer the suppressive dose of thyroxine needs to be increased by 26-38% which is slightly less than the increase of the replacement dose in hypothyroid pregnant women.

Downregulation of platelet-activating factor responsiveness during maturation of human dendritic cells.

Dendritic cells (DCs) are specialized antigen-presenting cells characterized by their ability to migrate into target sites, process antigens, and activate naive T-cells. Biological activities of platelet-activating factor (PAF) and the cytokine macrophage inflammatory protein-3beta (MIP-3beta) as well as the mRNA expression of their receptors were characterized in human DCs during lipopolysaccharide (LPS)-promoted maturation. Platelet-activating factor induced calcium transients, migration-associated actin polymerization response, and chemotaxis in immature human dendritic cells differentiated in vitro from monocytes with interleukin-4 and granulocyte macrophage colony stimulating factor. In addition, RT-PCR experiments indicated mRNA expression of the PAF receptor in these immature DCs. Cell studies and mRNA analyses further revealed that immature DCs neither respond to MIP-3beta nor express its specific receptor, CCR7. Induction of cell differentiation by LPS led to the loss of the mRNA expression of the PAF receptor, accompanied by decreasing intracellular calcium release, actin polymerization, and migration after stimulation with PAF. In contrast, LPS treatment induced increasing responsiveness toward MIP-3beta and mRNA expression of CCR7. Comparable data regarding mRNA expression of PAF receptor and PAF responsiveness were also obtained with another maturation protocol using TNFalpha instead of LPS. The direct comparison between the two different protocols showed a slower decrease of PAF responsiveness induced by TNFalpha than by LPS. These results show the loss of PAF responsiveness associated with downregulation of PAF receptor mRNA expression during LPS- and TNFalpha-induced maturation in human DCs. Therefore, these findings point to a functional relevance of PAF in recruiting immature DCs, whereas MIP-3beta might regulate the migration of DCs at a later stage of maturation.

A body-weight-independent dosing regimen of cyclosporine microemulsion is effective in severe atopic dermatitis and improves the quality of life.

BACKGROUND: Cyclosporine has shown to be effective in severe atopic dermatitis. Little has been reported on the new microemulsion form (Sandimmune, Neoral) in the treatment of this disease. Also, it has not been investigated whether a body-weight-independent dosing regimen of cyclosporine is appropriate for the treatment of atopic dermatitis. OBJECTIVE: The goal of this study was to investigate a body-weight-independent dosing regimen of cyclosporine microemulsion in severe atopic dermatitis by comparing high and low starting doses of treatment. METHODS: A total of 106 adults with severe atopic dermatitis were enrolled in this double-blind study and randomized to receive a starting dose of either 150 mg (low) or 300 mg (high) of cyclosporine microemulsion daily. After 2 weeks the dose could be reduced by 50% if the clinical symptom score was reduced by 50% or more. After 8 weeks the responders entered a 4-week follow-up phase and were randomized to either stop treatment or to continue on their last effective dose every second day. RESULTS: After 2 weeks of treatment the total symptom score decreased from 59.0 to 39.3 with 150 mg and from 60.7 to 33.2 with 300 mg cyclosporine (P <.05). Until week 8 there was a further decrease in the clinical symptom score to 30.8 with low-dose therapy and 25.5 with high-dose therapy. Similar positive effects could be observed in assessments of affected body surface area, itching, sleep loss, and quality of life. At week 2, there was an increase of 0.6% in serum creatinine in patients receiving 150 mg, and 5.8% in the 300 mg group (P <.01). At week 8, the effect on serum creatinine was similar, with a 1.1% rise in the low dose group and a 6.0% increase in the high dose group. Body weight had no influence on efficacy or tolerability in this study. CONCLUSION: Body-weight-independent dosing with cyclosporine seems to be feasible in the short-term treatment of severe atopic dermatitis. Although the starting dose of 300 mg/day is more effective than 150 mg/day, the 150 mg dose would be preferable for the initiation of therapy because of its excellent renal tolerability.

Metabolism and function of 3-D-phosphorylated phosphoinositides in C5a-stimulated eosinophils.

Eosinophils play a central role in the pathogenesis of parasitic infections, atopic diseases, and bullous dermatoses. To understand the regulative function of phosphatidylinositol 3-kinases in cell responses of eosinophils, phospholipid metabolism and production of reactive oxygen metabolites were followed after stimulation with C5a. Measurements of phosphatidylinositol lipids and analysis of deacylated products of separated lipid extracts showed fast and transient formation of phosphatidylinositol 3,4,5-trisphosphate (PIP(3)). Cell studies in the presence of the tyrosine kinase blocker genistein indicated that C5a-stimulated PIP(3) formation occurred independently of tyrosine kinase activity. To analyze the function of PI4,5P(2)-3-kinase in eosinophils, the influence of wortmannin and LY294002 on production of reactive oxygen metabolites was studied. Both compounds inhibited with similar concentration dependency C5a-induced formation of PIP(3) and production of reactive oxygen metabolites. In summary, these data showed for the first time the involvement of PI4,5P(2)-3-kinase in the production of reactive oxygen metabolites in eosinophils.

[Psychological status and motivation for psychosocial intervention in patients with allergic disorders]. / Psychisches Befinden und Motivation zu psychosozialen Interventionen bei Patienten mit allergischen Erkrankungen.

The aim of this study was to compare the psychological stress of patients with different forms of immediate type hypersensitivity and urticaria. Moreover, the patients' motivation for different forms of psychological treatment was assessed and an indication for psychosocial support was defined. 228 consecutive inpatients with insect venom allergies (ins), food intolerance (food), drug hypersensitivities (dru) and urticaria (urt) were evaluated by validated questionnaires regarding psychological strain and motivation for psychosocial treatments. Patients with food intolerance and urticaria showed significantly elevated psychological stress and higher motivation for psychosocial support as compared to those with insect venom allergies and drug intolerance. Patient education was the favourite technique for the patients (food 78%, urt 57%, dru 24%, ins 17%), followed by relaxation treatment. The most important predictors for the motivation were the wish for self-responsibility, a feeling of helplessness and social limitations. If strong indication criteria are applied, psychosocial support is indicated in only small subgroups of each patient group. In spite of that, the management of allergic disease should consider the potential need for psychosocial support.

Human eosinophils produce biologically active IL-12: implications for control of T cell responses.

The present study assessed the capacity of eosinophils (EOS) to synthesize the cytokine IL-12. Blood-derived, highly purified human EOS from six atopic patients and two nonatopic individuals were treated in culture with IL-4, IL-5, granulocyte-macrophage CSF, IFN-gamma, TNF-alpha, IL-1alpha, RANTES, and complement 5a, respectively. The expression of both IL-12 protein and mRNAs for the p35 and p40 IL-12 subunits was strongly induced in all donors by the Th2-like cytokines IL-4 and granulocyte-macrophage CSF and was also moderately induced by TNF-alpha and IL-1alpha. IL-5 treatment resulted in IL-12 synthesis in four atopic donors and one nonatopic donor, whereas IFN-gamma induced IL-12 synthesis in only two atopic donors. In contrast, RANTES exclusively induced mRNA for the p40 subunit without detectable protein release, and complement 5a had no effect on IL-12 mRNA or protein expression. EOS-derived IL-12 was biologically active, because supernatants derived from IL-4-treated EOS superinduced the Con A-induced expression of IFN-gamma by a human Th1-like T cell line. This activity was neutralized by anti-IL-12 Abs. In conclusion, EOS secrete biologically active IL-12 after treatment with selected cytokines, which mainly represent the Th2-like type. Consequently, EOS may promote a switch from Th2-like to Th1-like immune responses in atopic and parasitic diseases.

High-dose UVA1 therapy for atopic dermatitis: results of a multicenter trial.

BACKGROUND: The results of an open, single-center study suggested that phototherapy with high doses of UVA1 radiation (UVA1R; 340-400 nm) is effective for acute, severe exacerbations of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to assess the effectiveness of high-dose UVA1 phototherapy for acute, severe AD in a randomized multicenter trial in direct comparison with topical glucocorticoid therapy. METHODS: Patients were treated with high-dose UVA1R (10 days, 130 J/cm2/day; n = 20), topically with fluocortolone (10 days, 1 x daily; n = 17), or with UVA-UVB therapy (10 days, 1 x daily, minimal erythema dose-dependent; n = 16). RESULTS: With a clinical scoring system, significant differences in favor of high-dose UVA1R and fluocortolone therapy were observed (p < 0.0001), as compared with UVA-UVB therapy. At day 10, high-dose UVA1R was superior to fluocortolone (p < 0.002) therapy. Serum levels of eosinophil cationic protein and the blood eosinophil count were significantly reduced after high-dose UVA1 or fluocortolone, but not UVA-UVB therapy. CONCLUSION: This study confirms the therapeutic effectiveness of high-dose UVA1 monotherapy for treatment of severe exacerbations of AD.

Secondary adrenal insufficiency associated with autoimmune disorders: a report of twenty-five cases.

OBJECTIVE: Addison's disease is frequently a component of autoimmune polyendocrinopathies while secondary adrenal insufficiency associated with autoimmune disorders is believed to be a rare event. We present a series of patients with secondary adrenal insufficiency coexisting with autoimmune diseases and/or antithyroid autoantibodies. DESIGN AND PATIENTS: Among a group of 102 patients with secondary adrenal failure of unknown origin diagnosed at the Department of Endocrinology of the Centre for Postgraduate Medical Education (Warsaw, Poland) we have identified a group with associated autoimmune disorders. Thyroid abnormalities occurred most frequently. Other diseases included insulin-dependent diabetes mellitus, pernicious anaemia, vitiligo, premature ovarian failure and autoimmune thrombocytopaenia. There were 23 women and one man aged 17-72 years at the time of investigation. Additionally, we included a woman with Addison's disease in whom the ACTH deficiency appeared 18 years after the onset of primary adrenal hypofunction. MEASUREMENTS: Pituitary-adrenal function tests comprised urinary excretion of 17-hydroxycorticosteroids in basal conditions and during a 2-day tetracosactrin test, plasma concentrations of ACTH and cortisol, and a 2-day metyrapone test (in eight cases). Thyroid function and immunity tests were: TSH, thyroxine, the antithyroglobulin, antimicrosomal and anti-peroxidase autoantibodies. Other endocrine studies included: serum LH, FSH and PRL. RESULTS: The 17-hydroxycorticosteroid values, both basally and during stimulation tests were consistent with a diagnosis of secondary adrenal insufficiency. Serum cortisol and plasma ACTH concentrations were low. In 14 patients primary hypothyroidism was confirmed by low T4 levels. In three patients subclinical primary hypothyroidism was revealed (elevated TSH levels). Three patients who had a past history of Graves' disease were euthyroid at the time of investigation. Twenty-three patients had antibodies against peroxidase. Most patients had gonadotrophins and PRL values within normal limits. CONCLUSIONS: The co-existence of autoimmune disorders with secondary adrenal insufficiency suggests an autoimmune aetiology for the ACTH deficiency.

Treatment of chronic palmoplantar eczema with local bath-PUVA therapy.

BACKGROUND: Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema. Topical PUVA-paint avoids some of the unwanted side effects of systemic psoralens and has been used successfully in the treatment of palmoplantar eczema and psoriasis. However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema. OBJECTIVE: Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment. METHODS: After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen. Immediately after, the skin was irradiated with increasing doses of UVA, starting with 0.5 J/cm2. PUVA-bath therapy was performed 4 times a week up to a total of 25 treatments. No additional therapy was allowed except emollients. RESULTS: Excellent or good effects were achieved in 93% of the patients with dyshidrotic and in 86% of the patients with hyperkeratotic eczema. In the patients with dyshidrotic eczema, the cumulative doses and the highest single doses of UVA were lower than those in the patients with hyperkeratotic eczema (21.4 vs 27.9 J/cm2 and 2.4 vs 3.0 J/cm2 of UVA), but this was not statistically significant. No phototoxic reactions were observed. CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment. Compared with topical PUVA-paint, local bath-PUVA therapy has several advantages, particularly the absence of phototoxic reactions, severe hyperpigmentation, and protracted photosensitivity.

Evidence for the involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in CD18-mediated adhesion of human neutrophils to fibrinogen.

The CD18 integrin mediates chemotaxin-induced adhesion of neutrophils to fibrinogen. In neutrophils chemotaxins activate different intracellular pathways, which metabolize phosphatidylinositol 4,5-bisphosphate. To analyse the functional role of phosphatidylinositol 4,5-bisphosphate 3-kinase in the adhesion response, studies with the fungal metabolite wortmannin and the chemically unrelated compound LY 294002 were performed. These compounds inhibited with similar concentration dependency chemotaxin-induced formation of [32P]phosphatidylinositol 3,4,5-trisphosphate and CD18-mediated adhesion of neutrophils to fibrinogen, but did not influence expression of CD18 molecules at the cell surface. These data suggest involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in chemokine-induced avidity changes of CD18 integrins.

[Characterization of nonresponders in high dosage UVA1 therapy of acute exacerbated atopic dermatitis]. / Charakterisierung von Non-Respondern bei der hochdosierten UVA1-Therapie der akut exazerbierten Atopischen Dermatitis.

High-dose UVA1 therapy is an effective treatment of patients with acute atopic dermatitis. However, some patients do not respond well to this new therapy. We attempted to further characterize the non-responder population in a retrospective study. Two closely matched groups of responders (n = 20) and non-responders (n = 20) were compared. No significant differences were observed between both groups with respect to the following parameters: skin type, minimal erythema dose, single and cumulative doses of UVA1, and peripheral blood eosinophils. However, non-responders were characterized by a highly elevated atopic score, and by high levels of total IgE and of specific IgE. Furthermore, colonization of the skin with Staphylococcus aureus occurred at higher densities, and intestinal growth of Candida albicans was more frequently observed. These data indicate that high-dose UVA1 irradiation is not effective in all patients suffering from atopic dermatitis. We conclude that non-responders with complicating infections might benefit from the combination of high-dose UVA1 therapy and antibiotic or antimycotic treatment.

Chemotactic 5-oxo-eicosatetraenoic acids induce oxygen radical production, Ca2+-mobilization, and actin reorganization in human eosinophils via a pertussis toxin-sensitive G-protein.

The arachidonic acid metabolites 5-oxo-[6E,8Z,11Z,14Z]-eicosatetraen oic acid (5oETE) and 5-oxo-15-hydroxy-[6E,8Z,11Z,13E]-eicosatetrae noi c acid (5oHETE) are potent eosinophil chemotaxins. Here, the activation profile of 5-oxo-eicosanoids in eosinophils was further characterized and compared to other eosinophil activators such as complement fragment C5a (C5a), platelet-activating factor (PAF), interleukin-5 (IL-5), and phorbol ester (PMA). Flow cytometric studies revealed a rapid and transient actin polymerization upon stimulation by both 5-oxo-eicosanoids. Desensitization studies using actin polymerization as the parameter indicated cross-desensitization between the two 5-oxo-eicosanoids but revealed no interference with the response to other chemotaxins. Fluorescence measurements with Fura-2-labeled eosinophils in the presence of EGTA indicated Ca2+-mobilization from intracellular stores by 5oETE and 5oHETE. Both 5-oxo-eicosanoids stimulated the production of reactive oxygen metabolites as demonstrated by lucigenin-dependent chemiluminescence, superoxide dismutase-inhibitable cytochrome C reduction, and flow cytometric dihydrorhodamine-123 analysis. At optimal concentrations the changes induced by 5-oxo-eicosanoids were comparable to those obtained by C5a and PAF, whereas IL-5 and PMA induced only a restricted pattern of cell responses. Cell responses elicited by 5-oxo-eicosanoids were inhibited by pertussis toxin, indicating coupling of the putative 5-oxo-eicosanoid-receptor to G-proteins. These results indicate that 5-oxo-eicosanoids are stong activators of eosinophils with comparable biologic activity to the eosinophil chemotaxins C5a and PAF. These findings point to a role of 5-oxo-eicosanoids in the pathogenesis of eosinophilic inflammation as chemotaxins as well as activators of pro-inflammatory activities.

Evidence of the involvement of phosphatidylinositol 3-kinase in the migration, actin stress fiber formation, and alpha v beta 3-integrin-mediated adherence of human melanoma cells.

Tumor invasion and formation of metastases are major obstacles for a successful therapy of melanomas. Metastasis is thought to require multiple steps such as alpha v beta 3-integrin-mediated adhesion, proteolytic digestion of extracellular matrix by metalloproteinase-2, and reorganization of the actin cytoskeleton. To analyze the functional role of phosphatidylinositol 3-kinase in these processes, melanoma cells were treated with the fungal metabolite wortmannin. Wortmannin inhibited phosphatidylinositol 3-kinase activity in melanoma cells and migration in an equally concentration-dependent fashion. Flow cytometric analysis of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin-stained actin network indicated reduction of actin filaments by wortmannin. Fluorescence laser confocal microscopy experiments revealed breakdown of actin stress fibers. In addition, wortmannin inhibited alpha v beta 3-integrin-mediated adhesion of melanoma cells to vitronectin. Since flow cytometric measurements did not show altered expression of the alpha v beta 3-integrin at the cell surface, avidity changes of the alpha v beta 3-integrin by wortmannin are suggested. In contrast to the actin analysis and adhesion assays, wortmannin had no influence on mRNA expression or on protein secretion of metalloproteinase-2. These data provide evidence that phosphatidylinositol 3-kinase is an essential signal transduction protein required for migration of melanoma cells, regulating formation of the actin stress fiber as well as alpha v beta 3-integrin-mediated adhesion.

Recombinant human eotaxin induces oxygen radical production, Ca(2+)-mobilization, actin reorganization, and CD11b upregulation in human eosinophils via a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding protein.

The novel human CC-chemokine Eotaxin is a potent and selective chemotaxin for eosinophils. Here, the biological activities and the activation profile of Eotaxin were further characterized and compared with those of other eosinophil chemotaxins such as complement fragment C5a (C5a), platelet-activating factor (PAF), and RANTES in human eosinophils. Eotaxin stimulated the production of reactive oxygen metabolites as shown by lucigenin-dependent chemiluminescence and superoxide dismutase-inhibitable cytochrome C reduction. Furthermore, Eotaxin induced upregulation of the integrin CD11b. In addition, fluorescence measurements with Fura-2-labeled eosinophils in the presence of EGTA indicated Ca(2+)-mobilization from intracellular stores by Eotaxin. Flow cytometric studies showed rapid and translent actin polymerization on stimulation with Eotaxin. At optimal concentrations, the changes induced by Eotaxin were comparable with those obtained by C5a, PAF, and RANTES. Call responses elicited by Eotaxin were inhibited by pertussis toxin, indicating coupling of its putative receptor to heterotrimeric guanine nucleotide-binding proteins. These results indicate that Eotaxin is a strong activator of eosinophils with biological activity comparable with those of the eosinophil chemotaxins C5a, PAF, and RANTES. These findings point to a role of Eotaxin in the pathogenesis of eosinophilic inflammation as a chemotaxin as well as an activator of proinflammatory effector functions.

Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on the human mast-cell line (HMC)-1 by inflammatory mediators.

The effect of inflammatory mediators on the expression of several surface adhesion molecules on the human mast-cell line (HMC)-1 was studied. By flow cytometry, it could be shown that among several surface adhesion molecules (ICAM-1/CD54, VLA-4/CD49d, Mac-1/CD11b, LFA-1/CD11a, LFA-2/CD2, LFA-3/CD58, VCAM-1), only the constitutively expressed immunoglobulin family member intercellular adhesion molecule-1 (ICAM-1) is modulated by proinflammatory cytokines on HMC-1 mast cells. Stimulation with tumor necrosis factor-a (TNF-alpha) and interferon-gamma (IFN-gamma) resulted, in addition to interleukin-(IL-)4, in selective upregulation of ICAM-1 expression. Costimulation of either IL-4 or IFN-gamma with TNF-alpha further increased the ICAM-1 expression as compared to the stimuli alone. In contrast, stem-cell factor (SCF), granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-10, IL-8, monocyte chemotactic and activating factor (MCAF), and the complement split product C5a failed to modulate the expression of any adhesion molecule examined. The levels of cytoplasmic free calcium in HMC-1 mast cells were not altered by cross-linking surface ICAM-1, suggesting linkage of other intracellular signaling pathways. This cytokine-induced upregulation of ICAM-1 expression might reveal a putative regulatory mechanism of mast-cell interaction with effector cells bearing the counterparts of ICAM-1 (CD54), the molecules Mac-1 (CD11b/CD18) and leukosialin (CD43), and the principal ligand LFA-1 (CD11a/CD18).

Chemotactic 5-oxo-icosatetraenoic acids activate a unique pattern of neutrophil responses. Analysis of phospholipid metabolism, intracellular Ca2+ transients, actin reorganization, superoxide-anion production and receptor up-regulation.

Neutrophil cell responses and signal pathways elicited by the chemotactic arachidonic acid metabolites (6E, 8Z, 11Z, 14Z)-5-oxo-icosatetraenoic acid and (6E, 8Z, 11Z, 13E)-5-oxo-15-hydroxy-icosatetraenoic acid were studied and compared with those of other chemotaxins. Polyphosphoinositol lipid analysis revealed activation of phosphatidylinositol-biphosphate 3-kinase by both agonists. Experiments with Fura-2 in the presence of EGTA indicated Ca2+ mobilization from intracellular stores by both 5-oxo-icosanoids. A transient actin response and production of small amounts of superoxide anions upon stimulation with both agents was detected. The changes induced by 5-oxo-icosanoids were more moderate and transient than those obtained by other chemotaxins. Desensitization studies indicated cross-desensitization between both 5-oxo-icosanoids, but no interference with the response of other chemotaxins. All cell responses elicited by 5-oxo-icosanoids at concentrations 500-fold higher than the ED50 of other functions did not induce up-regulation of CD11b and N-formyl-peptide receptors at the cell surface, and failed to potentiate N-formyl-peptide-induced superoxide anion production. These results indicate that 5-oxo-icosanoids trigger a unique pattern of neutrophil responses.