Activated, not resting, platelets increase leukocyte rolling in murine skin utilizing a distinct set of adhesion molecules.
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.
Ludwig
Ralf J
RJ
Department of Dermatology, J.W. Goethe-University, Frankfurt, Germany. r.ludwig@em.uni-franfurt.de
Schultz
Jeanette E
JE
Boehncke
Wolf-Henning
WH
Podda
Maurizio
M
Tandi
Christa
C
Krombach
Fritz
F
Baatz
Holger
H
Kaufmann
Roland
R
von Andrian
Ulrich H
UH
Zollner
Thomas M
TM
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000502:physiology*; D015539:Platelet Activation; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology*; D011565:Psoriasis / Q000097:blood; D012867:Skin / Q000473:pathology*
D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019039:Platelet Glycoprotein GPIIb-IIIa Complex