No abstract

Lactadherin is a secreted extracellular matrix protein expressed in phagocytes and contributes to the removal of apoptotic cells. We examined lactadherin expression in brain sections of patients with or without Alzheimer's disease and studied its role in the phagocytosis of amyloid ␤-peptide (A␤). Cells involved in Alzheimer's disease, including vascular smooth muscle cells, astrocytes, and microglia, showed a time-related increase in lactadherin production in culture. Quantitative analysis of the level of lactadherin showed a 35% reduction in lactadherin mRNA expression in the brains of patients with Alzheimer's disease (n ‫؍‬ 52) compared with age-matched controls (n ‫؍‬ 58; P ‫؍‬ 0.003). Interestingly, lactadherin protein was detected in the brains of patients with Alzheimer's disease and controls, with low expression in areas rich in senile plaques and marked expression in areas without A␤ deposition. Using surface plasmon resonance, we observed a direct pro-

Astrocytes and one of their products, IL-6, not only support neurons but also mediate inflammation in the brain. Retinoidrelated orphan receptor-␣ (ROR␣) transcription factor has related roles, being neuro-protective and, in peripheral tissues, antiinflammatory. We examined the relation of ROR␣ to astrocytes and IL-6 using normal and ROR␣ loss-of-function mutant mice. We have shown ROR␣ expression in astrocytes and its up-regulation by pro-inflammatory cytokines. We have also demonstrated that ROR␣ directly trans-activates the Il-6 gene. We suggest that this direct control is necessary to maintain IL-6 basal level in the brain and may be a link between the neuro-supportive roles of ROR␣, IL-6, and astrocytes. Furthermore, after inflammatory stimulation, the absence of ROR␣ results in excessive IL-6 up-regulation, indicating that ROR␣ exerts an indirect repression probably via the inhibition of the NF-B signaling. Thus, our findings indicate that ROR␣ is a pluripotent molecular player in constitutive and adaptive astrocyte physiology.inflammation ͉ staggerer ͉ microglia

The specificities of autoantibodies directed against the acetylcholine receptor (AChR) for embryonic and adult muscle AChR were studied in 22 mothers with myasthenia gravis (MG) and in their newborns using human fetus and normal adult muscle AChR preparations. 12 mothers had transmitted MG to their neonates with, in three cases, antenatal injury. A clear correlation was found between occurrence of neonatal MG (NMG) and the high overall level of antiAChR antibodies (embryonic or adult muscle AChR). However, a strong correlation was also found between occurrence of NMG and the ratio of anti-embryonic AChR to anti-adult muscle (Te/Ta) AChR antibodies (P < 0.0002). Taken together, these data suggest that autoantibodies directed against the embryonic form of the AChR could play a predominant role in the pathogenesis of NMG. Paradoxically, the three cases with antenatal injury presumably the most severe form of NMG, were not associated with high Te/Ta. At the clinical level, these observations could prove helpful in the prediction of transmission of NMG. (J. Clin. Invest. 1994. 94:555-559.)