Time-dependent utilization of platelet arachidonic acid by the neutrophil in formation of 5-lipoxygenase products in platelet-neutrophil co-incubations.

The biosynthesis of leukotrienes is known to occur through a series of complex processes which, in part, can be influenced by cell-cell interactions. Several studies have suggested that arachidonic acid availability is a major limiting step for leukotriene biosynthesis and that its transfer between cells can represent a significant source of this precursor. Accordingly, effect of time and source of arachidonic acid on transcellular leukotriene synthesis was studied in mixed platelet/neutrophil populations challenged with the calcium ionophore A23187. A time-dependent contribution of platelet-derived as well as neutrophil-derived arachidonate was found in the selective formation of neutrophil 5-lipoxygenase metabolites. Utilization of platelet or neutrophil arachidonate was followed by incorporation of radiolabeled arachidonic acid into platelet or neutrophil phospholipids prior to stimulation. Specific activity of liberated arachidonic acid along with numerous 5-lipoxygenase products (including LTB4, 20-hydroxy-LTB4, 5-HETE and LTC4) was determined in order to follow mass and radiolabel. A large amount of platelet-derived arachidonic acid was released in the first 1.5 min, whereas 10 min platelet-derived arachidonate was much lower in amount but significantly higher in specific activity, suggesting different precursor pools. The platelet-derived arachidonate was heavily utilized by the neutrophils at the early time points for formation of 5-HETE and delta 6-trans-LTB4 isomers, but appeared to contribute only marginally to the constitutive metabolism of neutrophil arachidonate into LTB4. Results from these experiments suggest different pools of 5-lipoxygenase in the neutrophil and indicate a time and source dependent modulation of arachidonate metabolism in mixed cell interactions.

Role of leukotriene C4 and edema in the acute allergic bronchoconstriction in the guinea pig.

In vitro studies have suggested that leukotrienes are involved in acute allergic bronchoconstriction, though this has not been definitively corroborated yet in in vivo studies. On the other hand, edema production during antigenic challenge could be an additional factor favouring such bronchoconstriction. In the present work we quantified immunoreactive leukotriene C4 (iLTC4) concentrations in bronchoalveolar lavages during allergic bronchoconstriction induced by 1 mg/kg i.v. ovalbumin (OA) in immunized guinea pigs, as well as water content in guinea pig lung fragments obtained before and during this bronchoconstriction. We found that basal concentrations of iLTC4 (median 1.06 ng/ml) were not significantly modified at 2, 5 and 10 min (median 1.10, 0.29 and 1.37 ng/ml, respectively) of the bronchoconstrictor response. Water content in lung fragments did not change among non-immunized guinea pigs, immunized ones and at 15 min of bronchoconstriction (mean +/- SEM 79.32% +/- 0.18, 79.10% +/- 0.31 and 79.13% +/- 0.40%, respectively). In addition, isoproterenol (20 micrograms/kg, i.v.) rapidly reverted about 70% of the bronchoconstriction induced by a higher antigenic dose (OA, 3.1 mg/kg i.v.); residual obstruction was not associated with increased water content in lung fragments (78.13% +/- 0.43). These results suggest that in this model, acute allergic bronchoconstriction is not due to an increased iLTC4 release or to edema production, and that airway smooth muscle contraction is the main component of this response.

Estudo dos leucotrienos no humor aquoso e soro de pacientes portadores de uveítes e controles: análise de 93 casos / Study of leukotriene in aqueous humor and serum of patients with uveitis and controls: analysis of 93 cases

Foram estudados 93 pacientes sendo 59 com uveítes e 34 com patologias oculares, consideradas controles. As amostras de humor aquoso e soro foram analisadas para LTC4 por radioimunoensaio. Os resultados no humor aquoso foram signficantivamente maiores que no soro em todos os pacientes, sugerindo que houve produçäo intra ocular de leucotrienos. Näo houve diferença significativa entre os valores do humor aquoso das uveítes e controles, sugerindo que a produçäo intraocular de LT poderia ser decorrente de estimulaçäo pela paracentese ou entäo as patologias näo inflamatórias também poderiam estimular a síntese dod LTs. Os níveis de LTC4 näo mostraram relaçäo com a etiologias das uveítes. As uveites tiveram comportamento homogênio entre si com relaçäo ao tempo de história e atividade inflamatória. Determinou-se pela primeira vez o conteúdo sérico dos leucotrienos, que se mostrou existir, ao contrário do esperado. Demonstrou-se pela primeira vez que as células inflamatórias do humor aquoso de uveítes humanas säo capazes de produzir LTC4

Increased levels of leukotriene c4 in bronchoalveolar lavage from patients with pigeon breede's disease

En este estudio se midió la concentración de Leucotriene C4 (LTC4) y de complejos inmunes en el líquido obtenido po lavado broncoalveolar en pacientes con neumonitis por hipersensibilidad inducida por antígeno aviario (n=14), fibrosis pulmonar idiopática (n=5), neumonitis secundaria a artritis reumatoide (n=5), y en sujetos normales (n=4). Se encontró que los pacientes con neumonitis por hipersensibilidad tenían valores de LTC4 maiores que los sujetos normales (mediana, 5 ng/ml y 2.25 ng/ml, respectivamente) con p < 0.05, mientras que los pacientes con fibrosis pulmonar y artritis reumatóide tenían intermedios. Además, de 5 pacientes con neumonitis por hipersensibilidad y LTC4 < 4 ng/ml sólo uno tenía complejos inmunes elevados, mientras que de 9 pacientes con esta enfermedad y LTC4 > 4 ng/ml, 8 tenían complejos inmunes elevados (p < 0.03). Estos resultados sugieren que probablemente el LTC4 constituye uno de los mediadores biológicos que participan en la inflamación pulmonar de la neumonitis por hipersensibilidad inducida por antígeno aviario