Activated, Not Resting, Platelets Increase Leukocyte Rolling in Murine Skin Utilizing a Distinct Set of Adhesion Molecules
Autor: | J. Schultz, Wolf-Henning Boehncke, Thomas Matthias Zollner, Holger Baatz, Fritz Krombach, Ralf Ludwig, Maurizio Podda, Ulrich H. von Andrian, Christa Tandi, Roland Kaufmann |
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Jazyk: | angličtina |
Předmět: |
Psoriasis/blood
Blood Platelets Male Skin/*pathology skin Platelet Aggregation Leukocyte Rolling Inflammation Dermatology Platelet Glycoprotein GPIIb-IIIa Complex Biology Biochemistry Blood Platelets/*physiology Pathogenesis Mice medicine Leukocytes Animals Humans Platelet adhesion molecules Platelet activation Molecular Biology Membrane Glycoproteins Cell adhesion molecule Membrane Glycoproteins/*physiology Cell Biology P-Selectin/*physiology psoriasis Platelet Activation Leukocyte extravasation Molecular biology Mice Inbred C57BL P-Selectin Platelet Glycoprotein GPIIb-IIIa Complex/*physiology inflammation Immunology platelets Leukocytes/*physiology medicine.symptom homing Intravital microscopy |
Zdroj: | Journal of Investigative Dermatology, Vol. 122, No 3 (2004) pp. 830-836 |
ISSN: | 0022-202X |
DOI: | 10.1111/j.0022-202X.2004.22318.x |
Popis: | 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. |
Databáze: | OpenAIRE |
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