Ricin toxicity to microglial and monocytic cells

Microglial cells, like macrophages, are very sensitive to ricin, a galactos e-specific toxic lectin belonging to the family of ribosome-inactivating pr oteins. This toxin can be taken up by most cells through the binding of its B chain to galactose-containing molecules on the cell membrane. In macroph agic cell types it can be internalised also by mannose receptors which are present on the surface of these cells. Endocytosis of the toxin by either p athway was evaluated by ricin toxicity to primary cultures of rat microgial cells and to a microglial N11 cell line in the presence or absence of lact ose and mannan, which compete for the endocytosis via the ricin lectin chai n or cellular mannose receptors, respectively. Results were compared with t hose obtained in cultures of mouse macrophages, human monocytes, and a mono cytic JM cell line. All cultures were protected from ricin toxicity more by lactose than by mannan, indicating that ricin endocytosis via its lectin B chain is prevalent over that mediated by cellular mannose receptors. Howev er, a partial protection by mannan was observed in all cases but not-stimul ated NI I cells, either in the form of direct protection or of significant additional protection over that afforded by lactose. Mannose receptor expre ssion by NI I cells was negative before, and positive after, treatment with endotoxin, as assessed by the specific binding of I-125-mannose-bovine ser um albumin. Moreover, a partial protection from ricin toxicity by mannan wa s induced in the N11 microglial line after stimulation, consistently with a n inducible expression of the mannose receptor by activated cells switched towards a microglial phenotype. (C) 2001 Elsevier Science Ltd. All rights r eserved.