SDF- 1 -stimulated tethering, rolling, and arrest of nave CD4 + T - - PowerPoint PPT Presentation

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SDF- 1 -stimulated tethering, rolling, and arrest of nave CD4 + T - - PowerPoint PPT Presentation

Apr 23, 2023 139 likes •319 views

The state diagram of SDF- 1 -stimulated tethering, rolling, and arrest of nave CD4 + T lymphocytes Nicholas R. Anderson, Dooyoung Lee, and Daniel A. Hammer UPenn CBE GSS T cells at the forefront of cancer treatments 3 Liddy, et al ., Nat

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SLIDE 1

The state diagram of SDF-1α-stimulated tethering, rolling, and arrest of naïve CD4+ T lymphocytes

Nicholas R. Anderson, Dooyoung Lee, and Daniel A. Hammer

UPenn CBE GSS

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SLIDE 2

T cells at the forefront of cancer treatments

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Liddy, et al., Nat Med, 2012.

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SLIDE 3

Leukocyte adhesion cascade

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Adapted from Ley, Nat Rev Immunol, 2007.

Capture Activation Rolling Arrest Spreading Crawling Transmigration

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SLIDE 4

Simulated state diagram

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1 10 100 0.1 1 10 Selectin density (molecules/µm2) ICAM-1 density (molecules/µm2)

Adapted from Bhatia, et al, Biophys J, 2003.

Firm adhesion Rolling adhesion kf0,integrin = 10 s-1 kf0,integrin = 1000 s-1

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SLIDE 5

Experimental System

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Free flowing Capture Rolling Arrest

Protein A/G Pluronic F127 E-selectin ligands E-selectin CXCR4 SDF-1α LFA-1 ICAM-1

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SLIDE 6

Cellular motion

Tethering

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SLIDE 7

Cellular motion

Tethering Rolling

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SLIDE 8

Cellular motion

Tethering Rolling Arrest

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SLIDE 9

ICAM-1 only surfaces have high levels of tethering

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E-selectin enhances rolling

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SLIDE 11

Both E-selectin and ICAM-1 are required for efficient arrest

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SLIDE 12

Rolling velocity is constant across many surfaces

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ICAM-1 is required for stopping

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SLIDE 14

Connection to upstream migration?

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Conclusions

  • System allows for study of entire leukocyte adhesion cascade
  • E-selectin and ICAM-1 can act synergistically to promote arrest
  • Small numbers of E-selectin or ICAM-1 can rapidly change

prominent adhesion types

  • Naïve CD4+ T cells maintain constant rolling velocity across

many surface types

  • Time to stop can vary significantly depending on surface

composition

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SLIDE 16

Acknowledgements

Alex Buffone, Jr., PhD Woo Sik Jang, PhD Ben Schuster, PhD Katie Pulsipher, PhD Chen Gao Eric Wang Sarah Kim Ellen Reed Adam Suppes

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Hammer Lab