Endothelial Cell “Memory” of Inflammatory Stimulation: Human Venular Endothelial Cells Store Interleukin 8 in Weibel-Palade Bodies

Abstract

SummaryThe expression and secretion of interleukin (IL)-8, the prototype member of the C-X-C subfamily of chemokines, can be induced by diverse inflammatory stimuli in many cells, including endothelial cells (EC). Upon de novo synthesis, IL-8 localizes intracellularly in the Golgi apparatus, from where it is secreted. In addition to this constitutive secretory pathway, we describe a depot storage and separate regulated secretory pathway of IL-8 in EC.The prolonged stimulation of primary human EC with inflammatory mediators resulted in the accumulation of IL-8 in Weibel-Palade bodies, where it colocalized with von Willebrand factor. IL-8 was retained in these storage organelles for several days after the removal of the stimulus and could be released by EC secretagogues such as phorbol myristate acetate, the calcium ionophore A23187, and histamine. These findings suggest that storage of IL-8 in WeibelPalade bodies may serve as the EC "memory" of a preceding inflammatory insult, which then enables the cells to secrete IL-8 immediately without de novo protein synthesis.

Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice

“…These findings emphasize the importance of Weibel-Palade bodies at the interface between the inflammatory and the hemostatic response. In addition to their role in exposing P-selectin to the cell surface after endothelial cell activation, Weibel-Palade bodies may play a role in inflammation through IL-8, which has been reported as being stored in these granules in microvascular endothelial cells (23,24). Furthermore, in another inflammatory setting, atherosclerosis, Weibel-Palade bodies were found in great numbers at sites of lesions (25).…”

Reactive Oxygen Species in Inflammation and Tissue Injury

“…In contrast to selectin-mediated adhesion, which leads to the rolling of neutrophils, adhesion of leukocytes by b 2 integrins is firm and is regarded an essential step for transendothelial migration of inflammatory cells. b 2 -integrins are activated by chemokines such as CXCL1 (stored in small cytoplasmic granules) and CXCL8 (stored in Weibel-Palade bodies), which are secreted by endothelial cells (456,465). The binding of chemokines to chemokine receptors (CXCR1 and CXCR2) changes the conformation of integrins from bent to fully extended high-affinity configuration, enabling neutrophil arrest by binding to ICAM-1 that is expressed in endothelial cells (Fig.…”

lnterleukin-8 gene polymorphism and susceptibility to gastric cancer in a brazilian population

“…IL-8 is a chemokine produced by macrophages and other cells such as epithelial and endothelial cells (Wolff et al, 1998). This cytokine is involved in the infl ammatory response to infection with Helicobacter pylori, recruits phagocytes and causes damage to the gastric mucosa by inducing the release of reactive oxygen radicals (Torok et al, 2005;Ohyauchi et al, 2005).…”