L’élimination des cellules apoptotiques : une phagocytose particulière

Le programme de mort cellulaire par apoptose joue un rôle clé dans le maintien de l’homéostasie cellulaire. La première phase du programme conduit au démantèlement de la cellule. Celle-ci est très précocement reconnue et ingérée, par des phagocytes professionnels ou amateurs, grâce à la mise en œuvre d’une phagocytose spécialisée, l’engulfment ou engloutissement. Contrairement à l’attention portée aux mécanismes régissant la phase effectrice de l’apoptose, les bases moléculaires de l’engloutissement de la proie apoptotique ainsi que les conséquences physiologiques pouvant dériver d’une clairance sub-optimale n’ont été étudiées que récemment. Nous nous proposons de discuter ici les dernières avancées du domaine, ainsi que certains des attributs spécifiques de cette forme de phagocytose

Transition from dimers to higher oligomeric forms occurs during the ATPase cycle of the ABCA1 transporter.

Fluorescence resonance energy transfer and native PAGE analytical techniques were employed to assess the quaternary structure of ABCA1, an ATP binding cassette transporter playing a crucial role in cellular lipid handling. These experimental approaches support the conclusion that ABCA1 is associated in dimeric structures that undergo transition into higher order structures, i.e. tetramers, during the ATP catalytic cycle. Our data hence underline molecular assembly as a crucial parameter in ABCA1 function and the advantage of native PAGE as analytical tool for intractable membrane proteins

ABCA1 Gene Deletion Protects against Cerebral Malaria: Potential Pathogenic Role of Microparticles in Neuropathology

The ATP-binding cassette transporter A1 (ABCA1) modulates the transbilayer distribution of phosphatidylserine at the outer leaflet of the plasma membrane. This external exposure of phosphatidylserine is a hallmark of microparticle production and is impaired in ABCA1(−/−) mice. In this study, we report about the complete resistance to cerebral malaria of these mice. On analysis of histological and systemic parameters we evidenced an impairment of cellular responses to Plasmodium berghei ANKA infection in ABCA1(−/−) mice, as shown by lower plasma tumor necrosis factor levels, a weaker up-regulation of endothelial adhesion molecules in brain microvessels, a reduced leukocyte sequestration, as well as an ablated platelet accumulation. Besides, the number and the procoagulant activity of microparticles were dramatically reduced in the plasma of ABCA1(−/−) compared to ABCA1(+/+) mice. Moreover, microparticles derived from Plasmodium berghei ANKA-infected ABCA1(+/+) mice induced a significant increase of tumor necrosis factor release by noninfected macrophages. In ABCA1(−/−) mice platelet and macrophage responses to vesiculation agonists were ablated and reduced, respectively. Altogether, by pointing out the ABCA1 transporter as a major element controlling cerebral malaria susceptibility, these data provide a novel insight into its pathophysiological mechanisms and are consistent with a pathogenic role of microparticles in this neurological syndrome