The murine IL-8 homologues KC, MIP-2, and LIX are found in endothelial cytoplasmic granules but not in Weibel-Palade bodies

Abstract

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.

Endothelial histamine H 1 receptor signaling reduces blood–brain barrier permeability and susceptibility to autoimmune encephalomyelitis

“…In addition to their barrier function, endothelial cells store and release inflammatory mediators from Weibel-Palade bodies (WPBs) (42) and cytoplasmic granules (43). Although histamine is known to be a secretagogue for the release of WPB contents (44), our data do not support a role for H 1 R in triggering the inflammatory capacity of endothelial cells in the CNS.…”

Apoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor metastases in bone

“…All samples were analyzed by ELISA to measure 3 closely related cytokines: CXCL5, CXCL6 (a human cytokine homologous to mouse CXCL5), and IL-8 (CXCL8). Human IL-8 is a proinflammatory cytokine with no direct murine homolog, suggested to be functionally homologous with murine CXCL1, CXCL5, and CXCL6 (43). Intriguingly, normal samples displayed significantly higher serum CXCL5 relative to localized cancer samples ( Figure 12D).…”

Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil migration in mice

“…11 Cytokine-activated human endothelial cells synthesize the related chemokine IL-8, store it in regulated secretory granules, and release it in response to thrombin or histamine. 12,13 In vivo, murine endothelial cells store basal levels of CXCL1 in secretory granules, 14 and they express more CXCL1 in response to cytokines. 1,15 Extravascular cells also express chemokines, including CXCL1.…”