Leukocytes chemokine-induced transmigration

In other studies, intrapleural tetracycline was found to cause an acute and rapid rise in the level of interleukin-8, which correlated with the presence of neutrophils in pleural fluids of patients (50). In in vitro studies, we investigated whether talc stimulated pleural mesothelial cells to release C-X-C and/or C-C chemokines. We found that both IL-8 and MCP-1 release were induced in pleural mesothelial cells stimulated by talc (51). This release of chemokines is associated with several other phenomena including the expression of intracellular adhesion molecule-1 (ICAM-1). ICAM-1 is an adhesion molecule that binds with its natural ligand (CDl 1-CD18) receptors on leukocytes, which then transmigrate across the inflamed mesothelium into the pleural space in response to talc. Release of IL-8 and MCP-1 by talc-stimulated mesothelial cells required active phagocytosis of the talc particles by mesothelial cells. Inhibition of phagocytosis inhibited chemokine release. 

Figure 4.1. Schematic representation of leukocyte transmigration induced by chemokines. The first step involves rolling attributed to interaction between the leukocyte and the endothelial cells. This process is mediated by selectins and selectin ligands expressed on the surface of both cell types. In the next step a chemokine interacts with its receptor, inducing leukocyte activation and conformational changes in the adhesion molecules (integrins) and resulting in firm adhesion to the endothelial surface. It is believed that the chemokine is immobilized on the endothelial surface by interactions with glycosaminoglycans. The leukocytes then transmigrate into the tissues.

Intestinal inflammation In an animal model of Crohn s disease (hapten-induced cohtis), ZK-192 administered after disease onset displayed anti-inflammatory bioactions reducing TNF-, interferon-y and interleukin-8 LX modulates neutrophil transmigration across the intestinal epithelial monolayer, inhibits leukocyte rolling and adherence, modulates interleukin-8 release chemokine secretion LX inhibits TNl -o-induced nculrophil-cnlcrocyle interaction, chemokine release and colonocyte apoptosis Fiorucci et al. 2004... 

A rat model of ANCA disease has been induced by immunizing rats with human MPO, which induces anti-MPO antibodies that cross-react with human and rat MPO (66). As detected by intravital microscopy, rats with circulating anti-MPO resulting from active immunization or passive administration developed firm adherence and transmigration of leukocytes in the mesenteric microvasculature when a synergistic chemokine was apphed to exposed mesentery. Rats also developed focal hemorrhage in the mesenteric microvasculature at sites of chemokine application in the presence of circulating anti-MPO. 

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