Potentials of the Circulating Pruritogenic Mediator Lysophosphatidic Acid in Development of Allergic Skin Inflammation in Mice Role of Blood Cell-Associated Lysophospholipase D Activity of Autotaxin

作者：Shimizu Yoshibumi; Morikawa Yoshiyuki; Okudaira Shinichi; Kimoto Shigenobu; Tanaka Tamotsu; Aoki Junken; Tokumura Akira^*

来源：American Journal Of Pathology, 2014, 184(5): 1593-1603.

DOI：10.1016/j.ajpath.2014.01.029

Itching and infiltration of immune cells are important hallmarks of atopic dermatitis (AD). Although various studies have focused on peripheral mediator mediated mechanisms, systemic mediator-mediated mechanisms are also important in the pathogenesis and development of AD. Herein, we found that intradermal injection of Lysophosphatidic acid (LPA), a bioactive phospholipid, induces scratching responses by Institute of Cancer Research mice through LPA(1) receptor- and opioid mu receptor-mediating mechanisms, indicating its potential as a pruritogen. The circulating level of LPA in Naruto Research Institute Otsuka Atrichia mice, a systemic AD model, with severe scratching was found to be higher than that of control BALB/c mice, probably because of the increased lysophos-photipase D activity of autotaxin (ATX) in the blood (mainly membrane associated) rather than in plasma (soluble). Heparan sulfate proteogtycan was shown to be involved in the association of ATX with blood cells. The sequestration of ATX protein on the blood cells by heparan sulfate proteoglycan may accelerate the transport of LPA to the local apical surface of vascular endothelium with LPA receptors, promoting the hyperpermeability of venules and the pathological uptake of immune cells, aggravating Lesion progression and itching in Naruto Research Institute Otsuka Atrichia mice.

• 出版日期2014-5