The murine IL-8 homologues KC, MIP-2, and LIX are found in endothelial cytoplasmic granules but not in Weibel-Palade bodies.
Rapid translocation of P-selectin from WPB to the surface of endothelial cells is crucial for early neutrophil recruitment to acute inflammatory lesions. Likewise, the chemokine CXCL8/IL-8 is sorted to WPB in human endothelial cells, but little is known about its functional importance in lack of a suitable animal model. Here, we explored the distribution of the functional IL-8 homologues CXCL1/KC, CXCL2/MIP-2, and CXCL5-6/LIX in resting and inflamed murine vessels by confocal microscopy and paired immunostaining with markers of WPB, discovering that these chemokines did not localize to WPB but displayed a granular pattern in a subset of vessels in healthy skin compatible with sorting to the type 2 endothelial compartment for regulated secretion. Moreover, all chemokines colocalized with VWF and P-selectin in platelets, suggesting that their storage in platelet alpha-granules might represent an alternative source of rapidly available, neutrophil-recruiting chemokines. In conclusion, WPB appear not to be involved in regulated secretion of chemokines in the mouse, and instead, the possible existence of type 2 granules and the role of platelets in rapid leukocyte adhesion deserve further attention.
Hol
Johanna
J
Oslo University Hospital, Sognsvannsveien 20, 0027 Oslo, Norway.
Wilhelmsen
Linn
L
Haraldsen
Guttorm
G
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism*; D054426:Chemokine CXCL2 / Q000378:metabolism*; D054365:Chemokine CXCL5 / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016209:Interleukin-8 / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D020302:Weibel-Palade Bodies / Q000187:drug effects / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D054365:Chemokine CXCL5; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; C094739:Cxcl5 protein, mouse; D016209:Interleukin-8; D008070:Lipopolysaccharides; D019007:P-Selectin; D014841:von Willebrand Factor