Identification of 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid as a novel and potent human eosinophil chemotactic eicosanoid. (73/152)

Incubation of human eosinophils with arachidonic acid led to the formation of a novel and potent eosinophil chemotactic lipid (ECL) (Morita, E., Schroder, J.-M., and Christophers, E. (1990) J. Immunol. 144, 1893-1900). To test the working hypothesis of whether ECL could have been formed via eosinophil-arachidonic acid 15-lipoxygenase we investigated whether other arachidonic acid 15-lipoxygenases such as soybean lipoxygenase I catalyze formation of a similar ECL. In the presence of hemoproteins and soybean lipoxygenase I arachidonic acid is converted to an ECL, which has physicochemical properties similar to those found for the eosinophil-derived ECL. Purification of this ECL by high performance liquid chromatography revealed that ECL is structurally different from well known eosinophil chemotactic eicosanoids such as leukotriene B4, 5,15-(6E,8Z,11Z,13E)-dihydroxyeicosatetraenoic acid (5,15-diHETE), and (8S,15S)-(5Z,9E,11Z,13E)-dihydroxyeicosatetra eno ic acid ((8S,15S)-diHETE). UV spectra of this ECL with absorbance maxima at 230 and 278 nm revealed the presence of two independent chromophores such as a conjugated oxodiene and a conjugated diene. Catalytic hydrogenation of ECL methyl ester led to the formation of 5,15-dihydroxyarachidic acid methyl ester. Reduction of ECL with sodium borohydride produced a product which is identical with authentic (5S,15S)-(6E,8Z,11Z,13E)-diHETE. Formation of an ECL monomethoxime derivative supports the conclusion that this highly potent eosinophil chemotactic eicosanoid is structurally identical with 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid.  (+info)

Elevated levels of antimicrobial peptides in bronchoalveolar lavage fluid in patients with chronic eosinophilic pneumonia. (74/152)

BACKGROUND: Chronic eosinophilic pneumonia (CEP) is an idiopathic pulmonary disease. As the lung is in direct communication with the environment, inhaled antigen may activate immune mechanisms in the airway that may participate in the pathogenesis of idiopathic pulmonary diseases. Defensins are antimicrobial peptides that consist of alpha-defensin (HAD) in neutrophils and beta-defensin (HBD) in epithelial cells. Defensins act as innate immunity against pathogens acquired from the environment and as mediators to induce local inflammation. OBJECTIVES: The aim of the present study was to determine whether immune mechanisms in the airway are induced in CEP patients. METHODS: We measured BALF defensin levels in patients with CEP, acute EP (AEP) and drug-induced eosinophilic pneumonia (drug-EP). We also measured BALF levels of IL-5, GM-CSF, eotaxin and RANTES. These substances can recruit eosinophils. RESULTS: BALF HAD levels were higher in patients with CEP than in those with drug-EP and normal controls. HBD-2 was detected in BALF of 10 of 11 CEP patients and in 3 of 5 AEP patients while its level was below detection in drug-EP patients and normal controls. BALF HBD-2 levels correlated with the proportion of lymphocytes in CEP patients. CONCLUSION: The defensin-linked immune system is activated in CEP but not in drug-EP. This suggests that inhaled antigen(s) may be involved in the pathogenesis of CEP.  (+info)

Influence of age and gender on serum eotaxin concentration in healthy and allergic people. (75/152)

BACKGROUND: Eotaxin is one of the important chemokines that modulate allergic inflammation. In many studies a correlation between an elevated serum concentration of eotaxin, allergen exposure and allergic symptoms has been confirmed. Influence of other factors on eotaxin concentration is feebly recognized. We made an attempt to assess the influence of age and gender on the serum eotaxin level in healthy people and in patients with intermittent IgE-mediated rhinoconjunctivitis (AR). METHODS: The serum eotaxin level was measured in 245 healthy people and 241 patients with AR before the pollen season with the ELISA technique (KITS, R&D USA, pg/ml). The parametric tests and linear regression analysis were used in statistical calculations. RESULTS: There were no differences between the allergic group and the healthy one in the mean age (accordingly: 31.3 +/- 11.6 yrs. vs. 31.6 +/- 12.5 yrs.; p=0.1) and the mean serum eotaxin content (118.1 +/- 44.9 pg/ml vs. 116.3 +/- 34.8 pg/ml; p=0.3). A significant relationship between the serum eotaxin level, gender and age was revealed in both groups and regression models were derived. A linear correlation between age (semi-partial correlation beta = 0.47, p = 0.0000001) and gender (semi-partial correlation beta = 0.3, p = 0.0000001), on the one side, and the serum eotaxin level, on the other, was found for the allergic people. In the control group a similar relationship between the serum eotaxin level and age (semi-partial correlation coefficient beta = 0.63, p = 0.0000001) and gender (semi-partial correlation factor beta = 0.23, p = 0.000006) was observed. CONCLUSIONS: Age and sex significantly influence the serum eotaxin content in healthy people and patients with IgE-mediated rhinoconjunctivitis.  (+info)

Ontogeny of the production of an estrogen-regulated eosinophil chemotactic factor in the rat uterus. (76/152)

The ontogeny of an estrogen-induced eosinophil chemotactic activity in the uterus after estrogen administration and its regulation by progesterone was studied in neonatal rats at 3, 7, 10, and 13 days of age. These results were compared with the increase in peroxidase activity and the secretion of complement component C3 by the uterus. No chemotactic activity was observed in animals younger than 14 days, and after this age the estrogen regulation of the response was also prevented by the co-administration of progesterone. The secretion of complement C3 appeared earlier, at 10 days of age. It was also observed that the uterus of 3-7-day-old rats responded to estrogen by increasing the secretion of two proteins of 36 and 110 kDa. No further regulation or synthesis was observed with increasing age for these two proteins.  (+info)

Eosinophil chemotactic factor-L (ECF-L) enhances osteoclast formation by increasing in osteoclast precursors expression of LFA-1 and ICAM-1. (77/152)

ECF-L is a novel autocrine stimulator of osteoclast (OCL) formation that enhances the effects of 1,25-(OH)2D3 and RANK ligand (RANKL) and is increased in inflammatory conditions such as rheumatoid arthritis. ECF-L acts at the later stages of OCL formation and does not increase RANKL expression. Thus, its mechanism of action is unclear. Therefore, RAW 264.7 cells and M-CSF-dependent murine bone marrow macrophage (MDBM) cells were treated with RANKL and/or with recombinant ECF-L expressed as a Fc fusion protein (ECF-L-Fc) to determine their effects on NF-kappaB, AP-1 and JNK activity, and on the expression of the adhesion molecules that have been implicated in OCL formation. These parameters were measured by semiquantitative and PCR and Western blot analysis. In addition, the role of ICAM-1 was further assessed by treating normal mouse marrow cultures with ECF-L-Fc and 10(-10) M 1,25-(OH)2D3 in the presence or absence of a blocking ICAM-1 antibody or treating marrow cultures from ICAM-1 knockout mice with ECF-L and 1,25-(OH)2D3. ECF-L-Fc by itself only modestly increased NF-kappaB binding and JNK activity in RAW 264.7 cells, which was further enhanced by RANKL. In contrast, ECF-L-Fc increased LFA-1alpha and ICAM-1 mRNA levels 1.8-fold in mouse marrow cultures, and anti-ICAM-1 almost completely inhibited OCL formation induced by 10(-10) M 1,25-(OH)2D3 and ECF-L. Furthermore, ECF-L did not increase OCL formation in marrow cultures from ICAM-1 knockout mice. Taken together, these results demonstrate that ECF-L enhances RANKL and 1,25-(OH)2D3-induced OCL formation by increasing adhesive interactions between OCL precursors through increased expression of ICAM-1 and LFA-1.  (+info)

Toll-like receptor-2-mediated C-C chemokine receptor 3 and eotaxin-driven eosinophil influx induced by Mycobacterium bovis BCG pleurisy. (78/152)

An acute and persistent eosinophil infiltration is observed during Mycobacterium bovis BCG pleural infection in mice. Eosinophil accumulation, lipid body formation, and eotaxin production were significantly reduced in BCG-infected Toll-like receptor-2 (TLR2)-deficient mice compared to wild-type mice. Neutralization of eotaxin or CCR3 drastically inhibited BCG-induced eosinophil accumulation and lipid body formation, indicating that BCG-induced eosinophil recruitment and activation is largely dependent of TLR2-mediated eotaxin generation.  (+info)

Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. (79/152)

The increased numbers of activated eosinophils in the blood and tissues that typically accompany hypereosinophilic disorders result from a variety of mechanisms. Exciting advances in translating discoveries achieved from mouse models and molecular strategies to the clinic have led to a flurry of new therapeutics specifically designed to target eosinophil-associated diseases. So far, this form of hypothesis testing in humans in vivo through pharmacology generally has supported the paradigms generated in vitro and in animal models, raising hopes that a spectrum of novel therapies soon may become available to help those who have eosinophil-associated diseases.  (+info)

Mechanism of eosinophilic esophagitis. (80/152)

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