Alexander Crea

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The metabolism of leukotrienes (B4, C4, D4, and E4) within human plasma was studied and a simple sample preparation is presented. It was demonstrated that leukotriene E4 and leukotriene B4 were stable during incubation at 37 degrees C using the in vitro system. In contrast, leukotriene C4 was metabolized by gamma-glutamyl transpeptidase activities into(More)
1. Leukotriene (LT) B3 was prepared by total chemical synthesis and its identity was confirmed by nuclear magnetic resonance analysis and proton homonuclear plot of connectivities and chemical shift assignments. The effects of LTB3 on complement receptor enhancement, chemotaxis and lysozyme release in human neutrophils (PMN) were compared with those of LTB4(More)
Lipoxins are trihydroxytetraene metabolites which are derived from arachidonic acid through an interaction between different lipoxygenase pathways. Previous work has shown that lipoxin A4 (LXA4) inhibits the chemotactic responsiveness of neutrophils (PMN) to leukotriene B4. We have now assessed the structural determinants of the lipoxin A4 molecule which(More)
1. Lipoxin A4 (LXA4) and lipoxin B4 (LXB4) have been evaluated for their capacities to modulate neutrophil (PMN) migration and endothelial cell adherence using compounds prepared by total chemical synthesis. 2. Increased PMN migration was seen with concentrations of LXA4 from 10(-9) mol/l to 10(-7) mol/l. LXA4 was 100-fold less potent than leukotriene B4(More)
Incubation of eosinophils (EOS) with alveolar macrophage (AM) supernatants isolated from asthmatic subjects followed by stimulation with the calcium ionophore A23187 resulted in enhancement of the capacity of EOS to elaborate leukotriene C4 (LTC4) (mean enhancement 169 +/- 37%, n = 31). Pretreatment of EOS with AM supernatants derived from normal(More)
Bronchoalveolar lavage (BAL) was performed on 11 atopic patients with mild asymptomatic bronchial asthma and 11 healthy nonasthmatic volunteers. All asthmatic subjects had evidence of bronchial hyperresponsiveness to inhaled carbachol. The concentrations of leukotriene (LT) C4, LTD4, LTE4, LTB4, prostaglandin D2 (PGD2), platelet-activating factor (PAF) and(More)
Airways responsiveness to leukotriene (LT) C4, LTD4, LTE4, histamine, and methacholine have been studied in eight asthmatic and six normal subjects. Airways responsiveness to each bronchoconstrictor agonist was assessed by constructing cumulative dose-response curves, and the dose that produced a 35% decrease in specific airways conductance (PD35) was(More)
Lipoxins are biologically active trihydroxytetraene containing products derived from arachidonic acid that are formed by interactions between lipoxygenases. Although the lipoxins have been generated from mixed cell suspensions in vitro, it has not been established whether these products are synthesized in vivo. We have performed bronchoalveolar lavage (BAL)(More)
Lipoxins (LX) are trihydroxytetraene metabolites derived from arachidonic acid via an interaction between the 5- and 15-lipoxygenases. Preincubation of [3H] myo-inositol labeled PMN with 10-7M and 10-5M LXA4 for 1 minute at 37 degrees C resulted in a concentration dependent inhibition of the generation of [3H] IP3 and [3H] IP in cells subsequently(More)
Peripheral blood mononuclear cells (PBMC) were isolated from seven normal subjects, eight asthmatic subjects clinically sensitive to corticosteroids (CS), and eight asthmatic subjects clinically resistant to corticosteroids (CR). PBMC were cultured at 37 degrees C for 24 h in the absence or presence of 10(-16) to 10(-4) M hydrocortisone. Calcium ionophore(More)