Differential modulation of IL‐1‐induced endothelial adhesion molecules and transendothelial migration of granulocytes by G‐CSF

Abstract

Granulocyte colony stimulating factor (G‐CSF) is widely used for mobilization of haemopoietic stem cells into the peripheral blood. However, little is known about the mechanisms involved in mobilization and the immune modulatory effects of this growth factor. In this report we show that G‐CSF down‐regulated intercellular adhesion molecule 1 (ICAM‐1) induced by Interleukin‐1 (IL‐1) on human endothelial cells. Interestingly, the G‐CSF‐mediated down‐modulation of IL‐1‐induced ICAM‐1 appeared to be biphasic. In pharmacological concentrations (>300 ng/ml), and in dose ranges of plasma G‐CSF levels above that of non‐febrile healthy individuals (30 pg/ml), a significant decrease in surface ICAM‐1 could be observed. This could be explained, at least in part, by an increased autocrine G‐CSF production by endothelial cells in response to IL‐1 and exogenous G‐CSF. In contrast to ICAM‐1, IL‐1‐triggered VCAM‐1 expression was superinduced by G‐CSF with the optimal concentration of 30 pg/ml. To evaluate the functional significance of these findings, 51Cr adhesion assays with peripheral blood mononuclear cells (PBMC) or granulocytes known to lack the VCAM‐1 counter‐receptor very late antigen 4 (VLA‐4) and IL‐1‐stimulated endothelial cells, in the presence or absence of G‐CSF, were performed. G‐CSF could not inhibit the IL‐1‐induced adhesion of PBMC to endothelial cells, which may be due to the differential adhesion molecule modulation. In contrast, granulocyte adhesion induced by IL‐1 could effectively be blocked by co‐incubation with G‐CSF. Finally, G‐CSF also inhibited transendothelial migration of granulocytes through IL‐1‐activated endothelial cells in a concentration‐dependent manner.

Naive Monocytes Can Trigger Transendothelial Migration of Peripheral Blood Cells Through the Induction of Endothelial Tumour Necrosis Factor‐α

“…Figure 4 clearly demonstrates that the EAF in the SN of MM6 not only induced the endothelial adhesion molecules on HMEC, but also triggered the adhesion of MM6 to the endothelium as well as transendothelial migration, which resembles a prerequisite for local in¯ammatory responses in vivo. It has been reported previously that there is a strict correlation between the induction of endothelial ICAM-1 and the adhesion of peripheral blood cells and their transendothelial migration, respectively, as could be learned from ICAM-1 neutralization studies [9,10]. This could be con®rmed in the present study, coincubating SN of MM6 with an anti ICAM-1 MoAb, which led to a complete abrogation of the EAF mediated MM6 adhesion (data not shown), suggesting that, Fig.…”

“…Proin¯ammatory cytokines as well as bacterial endotoxin (LPS) are known to induce the ICAM-1 expression on endothelial cells and thereby promote a leuko-cyte±endothelial adhesion [2±8]. Previous work from our group [9,10] and many others have clearly shown that there is a close correlation between an increased ICAM-1 expression, adhesion of peripheral blood cells and their transendothelial migration.…”

Eosinophil peroxidase induces inflammation in a mouse model of dermatitis

“…TNF was recently shown by our group to stimulate eosinophilopoiesis after exposure to ozone (Wicher et al 2017), and increases expression of eotaxin in epithelial cells, a potent chemokine for eosinophils (Lilly et al 1997). IL-1 also directly stimulates expression of adhesion molecules on endothelial cells that eosinophils use to migrate into tissue (Eissner et al 1997).…”

Salmon consumption by pregnant women reduces ex vivo umbilical cord endothelial cell activation

“…Some growth factors are known to play an antiinflammatory role and exert protective effects on ECs (42,43). The salmon diet tended to increase the production of G-CSF by LPS-stimulated ECs.…”

“…The salmon diet tended to increase the production of G-CSF by LPS-stimulated ECs. Endogenous G-CSF is known to downregulate IL-1-induced ICAM-1 expression and granulocyte adhesion on human ECs (42). The concentration of G-CSF in HUVEC supernatant fluid of the salmon group on LPS stimulation was 4 times higher than in the corresponding control group, which may have been related to the antiinflammatory effects of the salmon diet.…”