Activated, not resting, platelets increase leukocyte rolling in murine skin utilizing a distinct set of adhesion
Ralf J Ludwig1, Jeanette E Schultz, Wolf-Henning Boehncke
1Department of Dermatology, J.W. Goethe-University, Frankfurt, Germany. r.ludwig@em.uni-franfurt.de
Abstract:
Selectin-mediated tethering and rolling initiates the multi-step process of leukocyte extravasation which is crucial for the formation of an inflammatory infiltrate. We studied the impact of platelets on this process in the skin. Using intravital microscopy, we analyzed platelet interactions with cutaneous post-capillary venules of mouse ears and observed an increase in platelet rolling if platelets were activated (41.6+/-20.2% vs. 13.1+/-8.5% rolling of resting platelets). Experiments with P-selectin deficient mice and antibodies blocking either P-selectin, GPIIb/IIIa or GPIb showed that rolling depends on platelet PSGL-1 and GPIIb/IIIa on one hand, and endothelial P-selectin on the other. Next, formation of platelet-leukocyte aggregates was demonstrated by simultaneous observation of platelets and leukocytes in vivo utilizing a newly developed two-color technique. Aggregates increased overall leukocyte rolling (leukocytes alone: 27.4+/-11.2%, leukocytes with resting platelets: 25.3+/-10.2%, leukocytes with activated platelets 38.1+/-11.8%). To investigate if activated platelets may contribute to the pathogenesis of chronic cutaneous inflammation, platelet P-selectin expression was studied in 8 patients with psoriasis. A correlation between platelet P-selectin expression and disease severity was established. In summary, we show that activated, not resting, platelets increase leukocyte rolling in murine skin. This increased rolling is due to the aggregate formation of platelets with leukocytes. We also provide evidence for a potential role of this mechanism in the pathogenesis of chronic inflammatory skin diseases.
Insights
Activated platelets enhance leukocyte rolling in skin by forming aggregates with leukocytes. This process, involving platelet P-selectin, may contribute to chronic inflammatory skin diseases like psoriasis.
Area of Science:
- Immunology
- Dermatology
- Hematology
Background:
- Leukocyte extravasation is critical for inflammatory responses.
- Platelet interactions with leukocytes are increasingly recognized in inflammation.
- The role of platelets in skin inflammation requires further elucidation.
Purpose of the Study:
- To investigate the impact of activated platelets on leukocyte rolling in the skin.
- To determine the molecular mechanisms underlying platelet-leukocyte interactions during rolling.
- To explore the potential role of platelet activation in chronic cutaneous inflammation.
Main Methods:
- Intravital microscopy of mouse ear skin to observe platelet and leukocyte behavior.
- Experiments using P-selectin deficient mice and blocking antibodies (anti-P-selectin, anti-GPIIb/IIIa, anti-GPIb).
- A two-color in vivo technique to visualize platelet-leukocyte aggregates.
- Measurement of platelet P-selectin expression in psoriasis patients.
Main Results:
- Activated platelets significantly increased leukocyte rolling compared to resting platelets.
- Leukocyte rolling was dependent on platelet PSGL-1 and GPIIb/IIIa, and endothelial P-selectin.
- Platelet-leukocyte aggregate formation was observed and correlated with increased leukocyte rolling.
- Elevated platelet P-selectin expression correlated with disease severity in psoriasis patients.
Conclusions:
- Activated platelets, through aggregate formation with leukocytes, enhance leukocyte rolling in murine skin.
- This mechanism highlights a potential contribution of activated platelets to the pathogenesis of chronic inflammatory skin diseases.
- Platelet P-selectin may serve as a biomarker for disease severity in conditions like psoriasis.
Related Concept Videos
01:22Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:26Acute Inflammation II: Cellular Phase