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2016 ; 14
(5
): e1002459
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Platelets Guide Leukocytes to Their Sites of Extravasation
#MMPMID27152726
Zuchtriegel G
; Uhl B
; Puhr-Westerheide D
; Pörnbacher M
; Lauber K
; Krombach F
; Reichel CA
PLoS Biol
2016[May]; 14
(5
): e1002459
PMID27152726
show ga
Effective immune responses require the directed migration of leukocytes from the
vasculature to the site of injury or infection. How immune cells "find" their
site of extravasation remains largely obscure. Here, we identified a previously
unrecognized role of platelets as pathfinders guiding leukocytes to their exit
points in the microvasculature: upon onset of inflammation, circulating platelets
were found to immediately adhere at distinct sites in venular microvessels
enabling these cellular blood components to capture neutrophils and, in turn,
inflammatory monocytes via CD40-CD40L-dependent interactions. In this cellular
crosstalk, ligation of PSGL-1 by P-selectin leads to ERK1/2 MAPK-dependent
conformational changes of leukocyte integrins, which promote the successive
extravasation of neutrophils and monocytes to the perivascular tissue.
Conversely, blockade of this cellular partnership resulted in misguided,
inefficient leukocyte responses. Our experimental data uncover a
platelet-directed, spatiotemporally organized, multicellular crosstalk that is
essential for effective trafficking of leukocytes to the site of inflammation.
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