CD33M inhibits microglial phagocytosis, migration and proliferation, but the Alzheimer's disease-protective variant CD33m stimulates phagocytosis and proliferation, and inhibits adhesion.

CD33 is a Siglec (sialic acid-binding immunoglobulin-type lectin) receptor on microglia. Human CD33 can be alternatively spliced into two isoforms: the long isoform (CD33M) and a shorter isoform (CD33m) that lacks the sialic acid-binding site. CD33m appears to protect against Alzheimer's disease; however, it remains unclear how. To investigate potential mechanisms by which CD33m may confer protection, we expressed the CD33m and CD33M isoforms of human CD33 in mouse BV-2 and human CHME3 microglial cells and assessed microglia functions. In the BV-2 cells, CD33M inhibited microglial phagocytosis of beads, synapses, debris and dead cells, while CD33m increased phagocytosis of beads, debris and cells. RNAi knockdown of the endogenous mouse CD33 increased phagocytosis and prevented CD33m's (but not CD33M's) effect on phagocytosis. CD33M increased cell attachment but inhibited cell proliferation, while CD33m did the opposite. We also found that CD33M inhibited cell migration. In human CHME3 cells, CD33M increased cell attachment, but inhibited phagocytosis, proliferation and migration, whereas CD33m did the opposite. We conclude that CD33M inhibits microglial phagocytosis, inhibits migration and increases adhesion, while CD33m increases phagocytosis, proliferation and inhibits adhesion. Thus, CD33m might protect against Alzheimer's disease by increasing microglial proliferation, movement and phagocytosis of debris and dead cells.

New insights into gene-specific management in cystic fibrosis from the 2012 European Cystic Fibrosis Conference.

35th European Cystic Fibrosis Conference The Convention Centre, Dublin, Ireland, 6-9 June 2012 More than 2400 delegates attended the 35th European Cystic Fibrosis Conference held in Dublin between 6 and 9 June 2012. More than 525 abstracts were presented at the conference. There were 30 symposia with four speakers at each, in addition to numerous workshops where researchers had the opportunity to present their work into scientific, clinical and psychological aspects of cystic fibrosis care. Keynote speakers provided state of the art lectures in two plenary sessions. This report highlights two important areas in the field of molecular genetics and the need for new and validated clinical trial end points.