Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles.

Polymorphonuclear leukocyte (PMN)-derived microparticles display inhibitory properties on target cells as assessed in vitro; since PMNs contain abundant amounts of the endogenous anti-inflammatory protein annexin 1 (AnxA1), we tested here whether biologically active AnxA1 could be present in PMN-derived microparticles. PMN adhesion to human umbilical vein endothelial cell (HUVEC) monolayers led to the generation of microparticles that contained AnxA1, as detected by Western blotting, flow cytometry, and mass spectrometry analyses. Addition of these microparticles to recipient PMNs prior to flow over HUVEC monolayers significantly inhibited cell adhesion, an effect abrogated by a neutralizing anti-AnxA1 antibody, or an antibody raised against the AnxA1 receptor, that is termed lipoxin A(4) receptor or ALX.

Activation of the annexin 1 counter-regulatory circuit affords protection in the mouse brain microcirculation.

The purpose of this study was to investigate the role of the homeostatic antiinflammatory axis centered on annexin 1 (AnxA1) in cerebral microvascular dysfunction and tissue injury associated with middle cerebral artery (MCA) occlusion and reperfusion. Intravital fluorescence microscopy was used to visualize the mouse cerebral microcirculation: AnxA1 null mice exhibited more white blood cell adhesion in cerebral venules than their wild-type counterparts, and this was accompanied by a larger cerebral infarct vol and worse neurological score. All parameters were rescued by delivery of human recombinant AnxA1.