Name: selectins in immune cell capture
Uploaded: 2023-04-30T11:56:02.000Z
Duration: 1 min 25 s
Channel: JoVE

Selektine sind Glykoproteine auf der Zelloberfläche, die Kohlenhydratliganden binden und an der vorübergehenden Zell-Zell-Adhäsion beteiligt sind.
Alle Selektine bestehen aus einer N-terminalen Lektindomäne und einer epidermalen Wachstumsfaktor- oder EGF-Domäne, die die Bindungsspezifität und -stärke regulieren.
Die Anzahl der sequenzerhaltenen Wiederholungen oder SCR-Domänen kann jedoch je nach Art des Selektions zwischen zwei und neun Wiederholungen variieren.
Die kurzen L-Selektine, die auf Immunzellen wie Lymphozyten exprimiert werden, helfen ihnen, in die Lymphknoten zu wandern, indem sie Liganden an die Endothelzellen binden.
Die größeren P-Selektine werden hauptsächlich auf Blutplättchen exprimiert. Sie helfen bei der Aggregation von Blutplättchen und Immunzellen an der Verletzungsstelle.
Ein dritter Typ, die sogenannten E-Selektine, wird zusammen mit P-Selektinen auf Endothelzellen während einer Immunantwort zeitlich exprimiert.
Diese Selektine bilden schwache, vorübergehende Wechselwirkungen mit frei fließenden Leukozyten und verlangsamen diese.
Die Leukozyten rollen dann entlang der Endotheloberfläche, wo andere Zelladhäsionsmoleküle helfen, sie in die entsprechenden Gewebemikroumgebungen zu rekrutieren – ein Prozess, der als Leukozyten-Homing bezeichnet wird.

<ol>
	<li>Borsig, Lubor. "Selektine bei der Krebsimmunität." Glykobiologie 28.9 (2018): 648-655.</li>
	<li>Gicht, Stéphanie, Pierre-Luc Tremblay und Jacques Huot. "Selektine und Selektinliganden bei der Extravasation von Krebszellen und der Organselektivität der Metastasierung." Klinische und experimentelle Metastasierung 25.4 (2008): 335-344.</li>
</ol>

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Selectins

Zelladhäsion ist ein wesentlicher Aspekt der Mehrzelligkeit. Während stabile Zellinteraktionen normalerweise zwischen Zellen desselben Typs auftreten, treten vorübergehende Zellinteraktionen zwischen Zellen unterschiedlicher Gewebetypen auf, beispielsweise zwischen Neutrophilen und Endothelzellen. Selectine sind eine Klasse von Zelladhäsionsmolekülen (CAMs), die Kohlenhydratliganden binden, um eine vorübergehende Zelladhäsion zu bilden. Es handelt sich um stäbchenförmige Proteine mit einem langen extrazellulären Teil variabler Länge, der in der Lektindomäne endet, einem Lektin vom C-Typ, das Kohlenhydrate nur in Gegenwart von Calciumionen bindet. Basierend auf ihrer Gewebespezifität und Länge werden drei Haupttypen von Selectinen identifiziert: L-Selectine, P-Selectine und E-Selectine.

Selektine in der Immunantwort

Die Endothelzellen, die die Blutgefäße auskleiden, exprimieren P-Selectine und speichern sie in den Vesikelkörperchen, den Weible-Palade-Körperchen. Während einer Entzündung werden diese Vesikel durch die Histaminstimulation schnell an die Zelloberfläche mobilisiert. Diese aktivierten Endothelzellen regulieren auch ihre E-Selectin- und P-Selectin-Gene hoch und bereiten sie so darauf vor, frei fließende Leukozyten aus dem Blutkreislauf zu rekrutieren.

Leukozyten wie Neutrophile und Eosinophile exprimieren Kohlenhydratliganden wie PSGL-1 auf ihrer Zelloberfläche. Die aus den Endothelzellen herausragenden langen Selektine können leicht mit diesen Liganden interagieren und die frei fließenden Leukozyten aus dem Blutkreislauf „fangen“. Selektine liegen zunächst in der geschlossenen Konformation vor und binden daher nur schwach an ihre Liganden. Wenn der Leukozyten jedoch entlangfließt, löst die Scherbeanspruchung dieser Wechselwirkungen die Öffnung der Selektine aus. Selektine in offener Konformation können stark an ihre Liganden binden und so zur Verlangsamung der Leukozyten beitragen.

Selektine bei Krebs

Metastasierte Krebszellen kapern den normalen Selectin-vermittelten Rekrutierungsprozess, um in gesundes Gewebe einzudringen. Diese metastatischen Zellen exprimieren die Kohlenhydratliganden auf ihrer Zelloberfläche und werden dadurch empfänglich für die Bindung an die Endothelzellen. Nach der Bindung können die Krebszellen das Blutgefäß durch einen Prozess namens Extravasation verlassen. Die Krebszellen können dann die neue Stelle infiltrieren und Sekundärtumoren erzeugen.

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Die Zelladhäsion ist ein wesentlicher Aspekt der Vielzelligkeit. Während stabile Zellinteraktionen in der Regel zwischen Zellen des gleichen Typs auftreten, ...

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Cell Biology

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selectins in immune cell capture

Selectins help cells make short, temporary contacts during immune responses. They are cell adhesion molecules that bind carbohydrate ligands on other cells. These rod-like proteins have a long outside region and end in a lectin domain, which binds carbohydrates only when calcium ions are present.

Three main selectins are known: L-selectin, P-selectin, and E-selectin. Their names reflect where they are found and how long they are. This tissue specificity helps explain why selectins act in certain cell interactions instead of making permanent attachments.

In blood vessels, endothelial cells line the vessel wall and use selectins to recruit leukocytes during inflammation. These cells store P-selectin in vesicular bodies called Weibel-Palade bodies. When histamine stimulates the cells, the vesicles move quickly to the cell surface. The activated endothelial cells also increase E-selectin and P-selectin gene expression, which prepares them to attract free-flowing leukocytes.

Leukocytes such as neutrophils and eosinophils carry carbohydrate ligands on their surface, including PSGL-1. Long selectins on endothelial cells can reach out and catch these moving cells from the bloodstream. Selectins start in a closed form, so they bind weakly at first. As the leukocyte keeps moving, shear stress from the interaction opens the selectin. In the open form, the selectin binds more strongly and slows the leukocyte down.

Cancer cells can also use this same pathway. Metastatic cancer cells display carbohydrate ligands on their surface and can bind endothelial cells. This lets them leave the blood vessel by extravasation and enter a new tissue. Once there, they can grow into secondary tumors.

Selectins in Immune Cell Capture

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selectins

Selectins help cells make short, temporary contacts during immune responses. They are cell adhesion molecules that bind carbohydrate ligands on other cells. These rod-like proteins have a long outside region and end in a lectin domain, which binds carbohydrates only when calcium ions are present. Three main selectins are known: L-selectin, P-selectin, and E-selectin. Their names reflect where they are found and how long they are. This tissue specificity helps explain why selectins act in...

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key terms and concepts

Learn how selectins help leukocytes slow down, how inflammation activates endothelial cells, and how metastatic cancer cells use the same pathway.

Selectins in Immune Cell Capture | JoVE K12

cell biology

JoVE Core Zellbiologie veranschaulicht komplexe zelluläre Prozesse in leicht verständlichen und dennoch umfassenden animierten Videolektionen. Diese Sammlung konzentriert sich auf die wesentlichen Bestandteile und Funktionen von Zellen, einschließlich Organellen und Membranen, Zelltransport und Zellenergie. Ergänzt wird sie durch Videos von Wissenschaftlern in Aktion, die die Anwendung der Zellbiologie in realen Forschungsexperimenten demonstrieren.

Selectins in Immune Cell Capture

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