Albumin stimulates monocyte chemotactic protein-1 expression in rat embryonic mixed brain cells

Albumin, a blood protein absent from the adult brain in physiological situations, can be brought into contact with brain cells during development or, in adult, following breakdown of the blood-brain barrier occurring as a result of local inflammation. In the present study, we show that ovalbumin and albumin induce the release of monocyte chemotactic protein 1 (MCP-1/CCL2) from rat embryonic mixed brain cells. A short-term exposure to ovalbumin during the cell dissociation procedure is sufficient to generate MCP-1 mRNA. A comparable effect is observed when the cells are incubated for 4 hr with ovalbumin or rat albumin, while MCP-1 messengers are barely detectable following bovine albumin exposure. The amount of MCP-1 protein measured in 4 hr-supernatants of albumin-treated cells followed the same albumin-inducing pattern as that of MCP-1 mRNA, while all albumins tested induced MCP-1 protein after a 17 hr-incubation period. The albumin-induced MCP-1 production is significantly inhibited in calphostin C-treated cells, suggesting the implication of a protein kinase C-dependent signaling pathway. This MCP-1-inducing activity is maintained after a lipid extraction procedure but abolished by proteinase K or trypsin treatments of albumin. The MCP-1 secretion following albumin contact with nervous cells could thus interfere, by chemotactic gradient formation, with the brain infiltration program of blood-derived cells during development or brain injury.