Possible Involvement of Sphingosine-1-Phosphate/G<sub>i</sub>/RhoA Pathways in Adherence of Eosinophils to Pulmonary Endothelium
-
- Sashio Toyokazu
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine
-
- Kume Hiroaki
- Department of Respiratory Medicine and Allergology, Kinki University Faculty of Medicine
-
- Takeda Naoya
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine
-
- Asano Toshiaki
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine
-
- Tsuji Seita
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine
-
- Kondo Masashi
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine
-
- Hasegawa Yoshinori
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine
-
- Shimokata Kaoru
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine
Bibliographic Information
- Other Title
-
- Possible Involvement of Sphingosine-1-Phosphate/Gi/RhoA Pathways in Adherence of Eosinophils to Pulmonary Endothelium
Search this article
Abstract
Background: Sphingosine-1-phosphate (S1P), a lysophospholipid released from inflammatory cells, causes cell migration by increasing cytokines and chemokines. This study was designed to determine whether S1P causes adherence of eosinophils to pulmonary endothelial cells via enhancement of adhesion molecule expression.<br> Methods: Expression of VCAM-1 and ICAM-1 was assessed by RT-PCR and Western blot analysis in human pulmonary microvasucular endothelial cells (HPMVECs). The number of adherent eosinophils to HPMVECs was calculated according to adhesion assay.<br> Results: Pre-treatment of HPMVECs with S1P increased mRNA and protein expression of VCAM-1, in contrast, did not dramatically increase those expression of ICAM-1. The maximal expression of these adhesion molecules in mRNA and protein was observed 4 and 8h after exposure to S1P, respectively. Pre-treatment with S1P also activated RhoA, a monomeric G protein; the ability of S1P to enhance the expression of VCAM-1 was attenuated by RhoA related inhibitors such as Y-27632, C3 exoenzyme, and GGTI-286. The effects of S1P on VCAM-1 were attenuated by pre-incubation with pertussis toxin, which catalyzes the ADP-ribosylation of Gi, a heterotrimeric G protein.<br> After HPMVECs were treated with S1P, adhesion of human eosinophilic leukemic cell line (EoL-1) cells to HPMVECs was enhanced in a concentration-dependent manner. Augmented adherence of EoL-1 cells by S1P was also attenuated by Y-27632 and pertussis toxin. S1P causes adherence of eosinophils to pulmonary endothelium via RhoA activation.<br> Conclusions: S1P may act as a lipid mediator in asthma. The RhoA/Rho-kinase pathway may be a therapeutic target for preventing eosinophil infiltration to the airway.<br>
Journal
-
- Allergology International
-
Allergology International 61 (2), 283-293, 2012
Japanese Society of Allergology
