Studies of Phospholipase A2 as a new target for treatment of bronchial asthma

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内科学一般
• Research Institution: Kinki University (2004); Tottori University (2002-2003)
• Principal Investigator: SANO Hiroyuki Kinki University, School of Medicine, Instructor, 医学部, 助手 (80325018)
• Co-Investigator(Kenkyū-buntansha): YAMASAKI Akira Tottori University, School of Medicine, Instructor, 医学部附属病院, 助手 (70325009) ; SANO Akiko Tottori University, School of Medicine, Instructor, 医学部, 助手 (80335512)
• Project Period (FY): 2002 – 2004
• Keywords: eosinophils / phospholipase A2 / bronchial asthma

Research Abstract

Cytosolic phospholipase A_2 (PLA_2) is the rate-limiting enzyme involved in the conversion of membrane phospholipids to arachidonic acid (AA) and lysophospholipids, which are readily metabolized to inflammatory mediators such as leukotrienes, thromboxane and platelet-activation factor. It has been recognized that receptor antagonists of leukotrienes or thronboxane are effective for treatment of bronchial asthma. To inhibit cPLA2 thus might be more effective than using leukotrienes or thronboxane receptor antagonist on treatment of bronchial asthma. We previously reported that cPLA2 regulates adhesion of human eosinophils to ICAM-1 or VCAM-1, and that inhibition of cPLA2 blocked eosinophil migration to lung tissue and antigen-induced airway hyperresponsiveness. In this study we investigated whether activity and quantitatition of cPLA2 in eosinophils from patients with asthma is more excessive than its from healthy donors.
Both AA release and cPLA2 activity from patients with asthma by 1□M FMLP were greater than its from healthy donors significantly. Quantitation of cPLA2 is 0.36±0.13 ng/10^6 cells from healthy donors and 0.52±0.17 ng/10^6 cells from patients with asthma(p=0.0285)