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

Le selectine sono glicoproteine della superficie cellulare che legano i ligandi dei carboidrati e partecipano all'adesione transitoria cellula-cellula.
Tutte le selectine comprendono un dominio lectina N-terminale e un fattore di crescita epidermico o dominio EGF che regolano la specificità e la forza del legame.
Tuttavia, il numero di ripetizioni conservate in sequenza o domini SCR può variare da due a nove ripetizioni a seconda del tipo di selectina.
Le L-selectine corte espresse sulle cellule immunitarie come i linfociti le aiutano a migrare nei linfonodi legando i ligandi sulle cellule endoteliali.
Le P-selectine più grandi sono espresse principalmente sulle piastrine. Aiutano ad aggregare le piastrine e le cellule immunitarie nel sito della lesione.
Un terzo tipo, chiamato E-selectine, è espresso temporalmente insieme alle P-selectine sulle cellule endoteliali durante una risposta immunitaria.
Queste selectine formano interazioni deboli e transitorie con i leucociti a flusso libero e li rallentano.
I leucociti rotolano quindi lungo la superficie endoteliale, dove altre molecole di adesione cellulare aiutano a reclutarli nei microambienti tissutali appropriati, un processo chiamato homing leucocitario.

<ol>
	<li>Borsig, Lubor. "Selectine nell'immunità al cancro". Glicobiologia 28.9 (2018): 648-655.</li>
	<li>Gotta, Stéphanie, Pierre-Luc Tremblay e Jacques Huot. "Selectine e ligandi della selectina nello stravaso di cellule tumorali e selettività d'organo delle metastasi". Metastasi cliniche e sperimentali 25.4 (2008): 335-344.</li>
</ol>

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Selectins

L’adesione cellulare è un aspetto essenziale della multicellularità. Mentre le interazioni cellulari stabili si verificano solitamente tra cellule dello stesso tipo, le interazioni cellulari transitorie si verificano tra cellule di diversi tipi di tessuto, come tra neutrofili e cellule endoteliali. Le selectine sono una classe di molecole di adesione cellulare (CAM) che legano i ligandi dei carboidrati per formare un'adesione cellulare transitoria. Sono proteine a forma di bastoncino con una lunga parte extracellulare di lunghezza variabile che termina con il dominio della lectina, che è una lectina di tipo C che lega i carboidrati solo in presenza di ioni calcio. Tre tipi principali di selectine vengono identificati in base alla specificità tissutale e alla lunghezza: L-selectine, P-selectine ed E-selectine.

Selectine nella risposta immunitaria

Le cellule endoteliali che rivestono i vasi sanguigni esprimono le P-selectine e le immagazzinano nei corpi vescicolari chiamati corpi di Weible-Palade. Durante l'infiammazione, la stimolazione dell'istamina mobilita rapidamente queste vescicole sulla superficie cellulare. Queste cellule endoteliali attivate sovraregolano anche i loro geni E-selectina e P-selectina, preparandoli così a reclutare leucociti a flusso libero dal flusso sanguigno.

I leucociti, come neutrofili ed eosinofili, esprimono i ligandi dei carboidrati, come PSGL-1, sulla loro superficie cellulare. Le lunghe selectine che sporgono dalle cellule endoteliali possono facilmente interagire con questi ligandi e "catturare" i leucociti a flusso libero dal flusso sanguigno. Le selectine sono inizialmente nella conformazione chiusa e quindi si legano debolmente ai loro ligandi. Tuttavia, mentre il leucocita scorre, lo stress di taglio di queste interazioni innesca l'apertura delle selectine. Le selectine in conformazione aperta possono legarsi fortemente ai loro ligandi e quindi aiutare a rallentare i leucociti.

Selectine nel cancro

Le cellule tumorali metastatiche dirottano il normale processo di reclutamento mediato dalla selectina per invadere i tessuti sani. Queste cellule metastatiche esprimono i ligandi dei carboidrati sulla loro superficie cellulare e quindi diventano ricettive per legarsi alle cellule endoteliali. Una volta legate, le cellule tumorali possono fuoriuscire dal vaso sanguigno, attraverso un processo chiamato stravaso. Le cellule cancerose possono quindi infiltrarsi nel nuovo sito, producendo tumori secondari.

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L'adesione cellulare è un aspetto essenziale della multicellularità. Mentre le interazioni cellulari stabili di solito si verificano tra cellule dello stesso tipo, le interazioni ...

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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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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

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Selectins in Immune Cell Capture

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