Pericytes support neutrophil transmigration via interleukin-8 across a porcine co-culture model of the blood–brain barrier

Pieper, Christian; Pieloch, Paulina; Galla, Hans‐Joachim

doi:10.1016/j.brainres.2013.05.047

Cited by 72 publications

(57 citation statements)

References 48 publications

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“…Another in vitro model showed that porcine brain PC are able to chemoattract neutrophils by CXCL8 after stimulation with LPS, TNF-α, or IL-1β (56). Remarkably, LPS-treated human brain PC showed a strong increase in the expression of both ICAM-1 and VCAM-1 which promoted a significant increase in adhesion of peripheral blood lymphocytes to human brain PC (45).…”

Section: Pericyte Control Of Immune Cell Traffickingmentioning

confidence: 99%

Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity

et al. 2016

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Pericytes (PC) are mural cells that surround endothelial cells in small blood vessels. PC have traditionally been credited with structural functions, being essential for vessel maturation and stabilization. However, an accumulating body of evidence suggests that PC also display immune properties. They can respond to a series of pro-inflammatory stimuli and are able to sense different types of danger due to their expression of functional pattern-recognition receptors, contributing to the onset of innate immune responses. In this context, PC not only secrete a variety of chemokines but also overexpress adhesion molecules such as ICAM-1 and VCAM-1 involved in the control of immune cell trafficking across vessel walls. In addition to their role in innate immunity, PC are involved in adaptive immunity. It has been reported that interaction with PC anergizes T cells, which is attributed, at least in part, to the expression of PD-L1. As components of the tumor microenvironment, PC can also modulate the antitumor immune response. However, their role is complex, and further studies will be required to better understand the crosstalk of PC with immune cells in order to consider them as potential therapeutic targets. In any case, PC will be looked at with new eyes by immunologists from now on.

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Section: Pericyte Control Of Immune Cell Traffickingmentioning

confidence: 99%

Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity

et al. 2016

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“…In contrast, little is known about the signals that regulate neutrophil migration across the BBB in acute neuroinflammation. Studies performed to specifically address this issue are sparse (25), and although unique mechanisms of neutrophil extravasation across of the BBB have already been suggested (26), consideration of flow has been omitted in these previous studies.…”

mentioning

confidence: 99%

β2 Integrin–Mediated Crawling on Endothelial ICAM-1 and ICAM-2 Is a Prerequisite for Transcellular Neutrophil Diapedesis across the Inflamed Blood–Brain Barrier

Gorina

Lyck

Vestweber

et al. 2014

The Journal of Immunology

146

128

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In acute neuroinflammatory states such as meningitis, neutrophils cross the blood–brain barrier (BBB) and contribute to pathological alterations of cerebral function. The mechanisms that govern neutrophil migration across the BBB are ill defined. Using live-cell imaging, we show that LPS-stimulated BBB endothelium supports neutrophil arrest, crawling, and diapedesis under physiological flow in vitro. Investigating the interactions of neutrophils from wild-type, CD11a−/−, CD11b−/−, and CD18null mice with wild-type, junctional adhesion molecule-A−/−, ICAM-1null, ICAM-2−/− , or ICAM-1null/ICAM-2−/− primary mouse brain microvascular endothelial cells, we demonstrate that neutrophil arrest, polarization, and crawling required G-protein–coupled receptor–dependent activation of β2 integrins and binding to endothelial ICAM-1. LFA-1 was the prevailing ligand for endothelial ICAM-1 in mediating neutrophil shear resistant arrest, whereas Mac-1 was dominant over LFA-1 in mediating neutrophil polarization on the BBB in vitro. Neutrophil crawling was mediated by endothelial ICAM-1 and ICAM-2 and neutrophil LFA-1 and Mac-1. In the absence of crawling, few neutrophils maintained adhesive interactions with the BBB endothelium by remaining either stationary on endothelial junctions or displaying transient adhesive interactions characterized by a fast displacement on the endothelium along the direction of flow. Diapedesis of stationary neutrophils was unchanged by the lack of endothelial ICAM-1 and ICAM-2 and occurred exclusively via the paracellular pathway. Crawling neutrophils, although preferentially crossing the BBB through the endothelial junctions, could additionally breach the BBB via the transcellular route. Thus, β2 integrin–mediated neutrophil crawling on endothelial ICAM-1 and ICAM-2 is a prerequisite for transcellular neutrophil diapedesis across the inflamed BBB.

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“…Primary BMECs of animal origin, including bovine (Salmeri et al, 2013), murine (Ludewig et al, 2013), and porcine (Pieper et al, 2013), have often been used to mimic the human BBB. While in vitro cell culture models share common characteristics with the human BBB, they are certainly not optimal or ideal.…”

Section: Discussionmentioning

confidence: 99%

Co-culture model consisting of human brain microvascular endothelial and peripheral blood mononuclear cells

Strazza

Maubert

Pirrone

et al. 2016

Journal of Neuroscience Methods

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Background Numerous systems exist to model the blood-brain barrier (BBB) with the goal of understanding the regulation of passage into the central nervous system (CNS) and the potential impact of selected insults on BBB function. These models typically focus on the intrinsic cellular properties of the BBB, yet studies of peripheral cell migration are often excluded due to technical restraints. New Method This method allows for the study of in vitro cellular transmigration following exposure to any treatment of interest through optimization of co-culture conditions for the human brain microvascular endothelial cells (BMEC) cell line, hCMEC/D3, and primary human peripheral blood mononuclear cells (PBMCs). Results hCMEC/D3 cells form functionally confluent monolayers on collagen coated polytetrafluoroethylene (PTFE) transwell inserts, as assessed by microscopy and tracer molecule (FITC-dextran (FITC-D)) exclusion. Two components of complete hCMEC/D3 media, EBM-2 base-media and hydrocortisone (HC), were determined to be cytotoxic to PBMCs. By combining the remaining components of complete hCMEC/D3 media with complete PBMC media a resulting co-culture media was established for use in hCMEC/D3 – PBMC co-culture functional assays. Comparison with existing methods Through this method, issues of extensive differences in culture media conditions are resolved allowing for treatments and functional assays to be conducted on the two cell populations co-cultured simultaneously. Conclusion Described here is an in vitro co-culture model of the BBB, consisting of the hCMEC/D3 cell line and primary human PBMCs. The co-culture media will now allow for the study of exposure to potential insults to BBB function over prolonged time courses.

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Pericytes support neutrophil transmigration via interleukin-8 across a porcine co-culture model of the blood–brain barrier

Cited by 72 publications

References 48 publications

Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity

Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity

β2 Integrin–Mediated Crawling on Endothelial ICAM-1 and ICAM-2 Is a Prerequisite for Transcellular Neutrophil Diapedesis across the Inflamed Blood–Brain Barrier

Co-culture model consisting of human brain microvascular endothelial and peripheral blood mononuclear cells

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