Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin.

Obstruction of airways by viscous sputum causes lung damage in patients with cystic fibrosis (CF). Sputum samples from CF patients were shown to contain filamentous actin. Human plasma gelsolin, a protein that severs actin filaments, rapidly decreased the viscosity of CF sputum samples in vitro. Gc globulin and deoxyribonuclease I, proteins that sequester monomeric actin but do not sever actin filaments, were less efficient than gelsolin in diminishing sputum viscosity. These results suggest that gelsolin may have therapeutic potential as a mucolytic agent in CF patients.

Coordinated inhibition of actin-induced platelet aggregation by plasma gelsolin and vitamin D-binding protein.

Actin is an abundant intracellular protein that is released into the blood during tissue injury and its injection into rats causes microthrombi to form in the vasculature. This report and others have shown that actin filaments are able to aggregate platelets in an adenosine diphosphate (ADP)-dependent manner. The effects on this process of two plasma actin-binding proteins, vitamin D-binding protein (DBP) and gelsolin, were examined separately and together. The addition of DBP, a monomer-binding protein, to actin filaments did not affect their ability to induce platelet aggregation. However, severing of actin filaments with gelsolin resulted in an increased degree of platelet aggregation. Preincubation of F-actin with both gelsolin and DBP resulted in a significant inhibition of aggregation. The effects of DBP and gelsolin on actin-induced aggregation paralleled their effects on exchange of actin-bound adenine nucleotides. DBP inhibited 1, N6-ethenoadenosine 5' triphosphate (epsilon-ATP) exchange with G-actin but not with F-actin. Gelsolin increased epsilon-ATP exchange with F-actin, which was largely abrogated by the addition of DBP. These results suggest that gelsolin's severing (and subsequent capping) of actin filaments not only results in an increase in the number of pointed filament ends but also in the dissociation of actin monomers containing ADP. Phalloidin, which stabilizes actin filaments while decreasing both monomer and nucleotide exchange, inhibited actin-induced aggregation, as well, indicating that depolymerization of actin filaments is not required to inhibit aggregation. Platelet activation by either G- or F-actin may thus be regulated by the local concentrations of the plasma actin-binding proteins gelsolin and DBP. Together, these proteins inhibit platelet aggregation in a manner that can be explained by their effects on actin's filament structure and the accessibility of its bound ADP. Depletion of DBP or gelsolin may allow actin released from injured tissues to stimulate purinergic receptors on platelets, and perhaps other cells, via its bound adenine nucleotides.

Presencia de receptores de estrógeno, progesterona y CBG en el tracto genital de ovejas y perras: estudio inmmunocitoquímico comparativo / Presence of estrogen and progesterone receptors and CBG in the female tract of sheep and dogs: comparative immunochemistry study

Los receptores esteroidales sexuales del tracto genital de la hembra tienen importancia ya que a través de ellos actúan las hormonas responsables de su desarrollo y de sus cambios morfofuncionales. Dado que en su mecanismo de control uno de los factores a tenerse en cuenta son las posibles diferencias entre las distintas especies, los objetivos de nuestro estudio fueron comparar en dos especies distintas la ovina (O) (n=6) y la canina (P) (n=6) la presencia de receptores de estrógenos (RE), progesterona (RP) y de CBG en ovario, tuba uterina y útero de hembras prepúberes (O:n=3; P:n=·3) y adultas (O:n=3; P:n=3). Se realizaron tinción con H-E e inmunocitoquimica según técnica de Stenberger. Los resultados revelaron: en ambas especies en animales durante el ciclo estral inmunorreactividad (IR) positiva marcada para estrógenos en útero, oviducto y ovario siendo comparativamente los RE más numerosos en oviducto de perra que en oveja. En ambos animales en anestro, la IR para RE fue negativa o leve en útero, no evidenciándose su presencia en otros órganos. Los RP variaron según el estadio del ciclo, no mostrando diferencias destacables entre las especies. En las hembras prepúberes de oveja fueron detectados RE Y RP, mientras que en perras éstos no fueron evidenciados. La CBG mostró IR positiva en el tracto de ambos animales durante el ciclo y fue negativa en prepúberes para ambas especies. Se concluye que existen diferencias, especialmente en hembras prepúberes, donde la presencia de RE y RP es detectable en ovejas no así en perras, siendo además, la presencia de RE comparativamente más marcada en tuba uterina de perra en ciclo que en oveja en el mismo estadio.

The sexual steroid receptors of the genital tract of the female has importance since on them the hormones responsible for their development and morphofuncional changes act. Due that in their control mechanism one of the factors to be kept in mind is the possible differences among the diverse species. The objective of our study was to compare in two different species sheep (O) ( n=6) and canine (P) ( n=6) the presence of receptors of estrogens (RE), progesterone (RP) and the presence of CBG in ovary, oviduct and uterus of female prepúberes (O:n=3; Pn=·3) and mature: (O:n=3; Pn=·3) We use H-E tint and and inmunocito chemistry according to technique of Stenberger. The results revealed: in both species of animals during the estral cycle: Inmunorreactivity (RI) positive marked for estrogens in uterus, oviduct and ovary being comparatively much more numerous RE in dog oviduct that in sheep. In both animals in anestro RE was negative or light in uterus, without evidenced of their presence in other organs. The RP varied according to the stage of the cycle not showing remarkables differences among the species. In the prepuber female sheep RE and RP were detected while in dogs they were not evidenced. The CBG showed positivity in the tract of both animals during the cycle and it was negative in both prepuber species We concludes that differences exist especially in prepuber female where the presence of RE and RP are detectable in sheep and no detectable in dogs, being further the comparatively presence of RE in dog oviduct in cycle more marked that in sheep in the same stage.