Monocyte chemoattractant protein-1 and the blood-brain barrier

Abstract

The blood-brain barrier (BBB) is a dynamic structure that maintains the homeostasis of the brain and thus proper neurological functions. BBB compromise has been found in many pathological conditions, including neuroinflammation. Monocyte chemoattractant protein-1 (MCP1), a chemokine that is transiently and significantly up-regulated during inflammation, is able to disrupt the integrity of BBB and modulate the progression of various diseases, including excitotoxic injury and hemorrhage. In this review, we first introduce the biochemistry and biology of MCP1, and then summarize the effects of MCP1 on BBB integrity as well as individual BBB components.

Fig. 1

Proposed model for MCP1-induced BBB compromise. By binding to CCR2, MCP1 induces phosphorylation of ERM proteins, which then bind to ZO-1 and actin cytoskeleton. Additionally, MCP1 also activates Rho-associated kinases, which phosphorylate and inactivate MLCP, resulting in increased phosphorylation of MLC. The over-phosphorylation of MLC induces enhanced and prolonged actin–myosin contraction, which generates forces that pull ZO-1 away from the cell–cell border, leading to BBB compromise. Adapted from [71]