Exposición a contaminantes ambientales y patología respiratoria Exposure to environmental contaminants & respiratory pathology

Objetivo: Tras la aparición de 5 casos con sintomatología respiratoria en una empresa aeronáutica y su exposición a diferentes sustancias químicas, nos propusimos investigar su posible relación con el medio laboral. Material y métodos: Se realizaron mediciones ambientales de polvo de aluminio, tricloroetileno y glicol, estudio alergológico con dichas sustancias además de neumoalergenos y tests epicutáneos con batería estándar europea, análisis de sangre, radiografías de tórax, mediciones de flujo pico y pruebas funcionales respiratorias, test de metacolina y electrocardiograma. Resultados: La medición del flujo pico y el test de hiperreactividad bronquial directo con metacolina fueron negativos. El estudio alergológico de las sustancias expuestas fue negativo detectándose en 3 casos resultados positivos a neumoalergenos. Conclusiones: La negatividad en las mediciones del flujo pico y el test de metacolina estando el trabajador en activo, prácticamente descartarían un cuadro de asma laboral, en la actualidad. No podemos descartar la posibilidad concomitante de un Síndrome de disfunción reactiva de la vía aérea en un momento previo al estudio. En tal caso, la existencia de una hiperreactividad bronquial inicial podría haber cedido sin llegar a objetivarse en la actualidad con metacolina. La creación de equipos multidisciplinarios es fundamental para la detección de enfermedades respiratorias de posible origen laboral.Target: After the appearance of 5 cases with respiratory symptoms in an aeronautical company and their exposal to different chemical substances, we proposed to investigate their possible link with the working environment. Material and methods: Aluminium environmental dust measurements, trichloroethylene and glycol, alergic study with these substances as well as with aero alergens and epicutaneos tests with a european standard accumulator were made, blood analysis, thorax x-rays, peak-flow measurements and functional respiratory tests, Methacholine test and electrocardiogram. Results: The peak-flow measurement and the direct bronchial hyperactivity test using metacholine were negative. The alergic tests performed were generally negative with the exception of 3 positive results concerning aero alergens test. Conclusions: The negative results of the peak-flow measurements and the metacholine test of an active worker, would practically disguard a cadre of work related asthma, at the present time. We cannot discard the concomitant possibility of a reactive disfunction syndrome via the aerial route in a precise moment of time previous to the study. In such case, the existence of an initial bronchial hyperreactivity could have yielded finally not being detectable with metacholine. The creation of multidisciplinary equipment is fundamental for the detection of respiratory diseases of possible work origin

A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling

The adaptor protein linker for activation of T cells (LAT) has an essential role transducing activatory intracellular signals coming from the TCR/CD3 complex. Previous reports have shown that upon T-cell activation, LAT interacts with the tyrosine kinase Lck, leading to the inhibition of its kinase activity. LAT–Lck interaction seemed to depend on a stretch of negatively charged amino acids in LAT. Here, we have substituted this segment of LAT between amino acids 113 and 126 with a non-charged segment and expressed the mutant LAT (LAT-NIL) in J.CaM2 cells in order to analyze TCR signaling. Substitution of this segment in LAT prevented the activation-induced interaction with Lck. Moreover, cells expressing this mutant form of LAT showed a statistically significant increase of proximal intracellular signals such as phosphorylation of LAT in tyrosine residues 171 and 191, and also enhanced ZAP70 phosphorylation approaching borderline statistical significance (p = 0.051). Nevertheless, downstream signals such as Ca2+ influx or MAPK pathways were partially inhibited. Overall, our data reveal that LAT–Lck interaction constitutes a key element regulating proximal intracellular signals coming from the TCR/CD3 complex