The role of asbestos bodies (and associated proteinacious coating) in asbestos associated diseases is not well understood. Currently employed methods of isolation of these bodies employ harsh chemicals that lead to destruction of their proteinacious coating. In this work a method was developed that enabled the purification of whole, integral, unmodified asbestos bodies (AB) by exploiting their magnetic properties. Albumin and ferritin were found to be the major proteins associated with AB isolated from lung tissue of mesothelioma patients. Magnetically isolated AB were shown to be cytotoxic and to activate free radical production from inflammatory cells at a higher extent than that induced by bodies obtained by chemical digestion. The finding that hypochlorite-treated AB induce DNA damage, while AB obtained by the method described in this article failed to do so, together with the differential behavior of these bodies toward inflammatory cells, suggests that native asbestos bodies should be used to investigate the pathogenetic role of these structures.

No abstract

No abstract

J. Neurochem. (2012) 122, 557–567. Abstract ATP‐activated P2X3 receptors of sensory ganglion neurons contribute to pain transduction and are involved in chronic pain signaling. Although highly homologous (97%) in rat and human species, it is unclear whether P2X3 receptors have identical function. Studying human and rat P2X3 receptors expressed in patch‐clamped human embryonic kidney (HEK) cells, we investigated the role of non‐conserved tyrosine residues in the C‐terminal domain (rat tyrosine‐393 and human tyrosine‐376) as key determinants of receptor function. In comparison with rat P2X3 receptors, human P2X3 receptors were more expressed and produced larger responses with slower desensitization and faster recovery. In general, desensitization was closely related to peak current amplitude for rat and human receptors. Downsizing human receptor expression to the same level of the rat one still yielded larger responses retaining slower desensitization and faster recovery. Mutating phenylalanine‐376 into tyrosine in the rat receptor did not change current amplitude; yet, it retarded desensitization onset, demonstrating how this residue was important to functionally link these two receptor states. Conversely, removing tyrosine from position 376 strongly down‐regulated human receptor function. The different topology of tyrosine residues in the C‐terminal domain has contrasting functional consequences and is sufficient to account for species‐specific properties of this pain‐transducing channel.

Following i.v. BCG infection, a new population of macrophages are recruited in the rabbit lung. These macrophages, known as activated macrophages, substitute the resident macrophages and can play a key role in the defence against mycobacteria. We report here that BCG-activated alveolar macrophages are equipped with a more active hexose monophosphate pathway, which can maintain an optimal intracellular concentration of NADPH and GSH, and allow to produce mycobactericidal free radicals and to become resistant to mycobacterium-induced programmed cell death. These findings suggest that sustaining the anti-oxidant properties of macrophages could represent a candidate process to be considered as a good therapeutic target in fighting Mycobacterium spp infections.

No abstract

No abstract