Rod-Shaped Monocytes Patrol the Brain Vasculature and Give Rise to Perivascular Macrophages under the Influence of Proinflammatory Cytokines and Angiopoietin-2

Abstract

The nervous system is constantly infiltrated by blood-derived sentinels known as perivascular macrophages. Their immediate precursors have not yet been identified in situ and the mechanism that governs their recruitment is mostly unknown. Here, we provide evidence that CD68 ϩ GR1 Ϫ monocytes can give rise to perivascular macrophages in mice suffering from endotoxemia. After adhesion to the endothelium, these monocytes start to crawl, adopt a rod-shaped morphology when passing through capillaries, and can manifest the ability to proliferate and form a long cytoplasmic protuberance. They are attracted in greater numbers during endotoxemia by a combination of vasoregulatory molecules, including TNF (tumor necrosis factor), interleukin-1␤, and angiopoietin-2. After a period of several hours, some of them cross the endothelium to expand the population of perivascular macrophages. Depletion of adherent monocytes and perivascular macrophages can be achieved by injection of anti-angiopoietin-2 peptide-Fc fusion protein. This study extends our understanding of the behavior of monocytes at the blood-brain interface and provides a way to block their infiltration into the nervous tissue under inflammatory conditions.

The Effects of Hypoxia on U937 Cell Line in Mesenchymal Stem Cells Co-Culture System

“…27 Hypoxia lead to CD49d upregulation, which lead to transmigration of monocytes. 28,29 Contrary, our findings showed, CD49d expression was down-regulated in presence of UCBMSCs ( Figure 5) (*P<0.05). …”

α1-Adrenergic Receptors Positively Regulate Toll-Like Receptor Cytokine Production from Human Monocytes and Macrophages

“…Increased IL-1␤ from innate immunocompetent cells have been implied in the pathogenesis of rheumatoid arthritis, type 1 diabetes, multiple sclerosis, and Alzheimer's disease (Licastro et al, 2000;Audoy-Rémus et al, 2008;Capellino and Straub, 2008;Bradshaw et al, 2009). Therefore, ␣ 1 -AR modulation of TLR4 signaling characterized in our investigations may prove to be a useful therapeutic strategy for the management of human diseases with known chronic inflammatory etiologies.…”

Functional Recovery after Peripheral Nerve Injury is Dependent on the Pro-Inflammatory Cytokines IL-1β and TNF: Implications for Neuropathic Pain

“…For immunohistological analysis, monocytes/macrophages were identified based on their expression of the iba1 marker (Boivin et al, 2007;Audoy-Rémus et al, 2008). Expression of the 7/4 antigen and nuclear morphology (i.e., round, ovoid, or kidney-shaped nucleus that occupies up to 50% of the overall cell area) were further used to define the population of M1 macrophages, as described previously (Henderson et al, 2003;Gordon and Taylor, 2005;Tsou et al, 2007).…”

“…Three-dimensional reconstructions of leukocytes were generated from confocal image stacks acquired using an Olympus Fluoview microscope (BX61) using the Imaris software (v. 4.5; Bitplane), following the method described previously (Audoy-Rémus et al, 2008).…”