MCP HAHNEMANN SCHOOL OF MEDICINE

MCP 哈内曼医学院

• 批准号: 6031907
• 负责人: JOHN S BOMALASKI
• 金额: $ 3万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-11-01 至 2000-11-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6031907
• 关键词: antisense nucleic acid; complementary DNA; enzyme activity; enzyme induction /repression; human subject; inflammation; interleukin 1; leukotrienes; molecular cloning; oligonucleotides; phospholipase A2; protein purification; protein sequence; protein structure function; rheumatoid arthritis; tumor necrosis factor alpha

DESCRIPTION: (Adapted from the applicant's abstract) Inflammation in many settings appears to be mediated by and/or amplified by phospholipase. This investigator and his colleagues have shown enhanced phospholipase A2 enzyme activities in cells and synovial fluid from patients with rheumatoid arthritis. They have also discovered and characterized a phospholipase A2 activating protein (PLAP) and have demonstrated the consequences of this protein on cells and phospholipase A2. They have shown that injection of PLAP into rabbit joints has resulted in an inflammatory arthritis response which closely resembles rheumatoid arthritis. In addition, exposure of peripheral blood leukocytes to PLAP has resulted in an eicosanoid and superoxide generation along with cellular degranulation. They have recently cloned and obtained the cDNA for PLAP. They also have generated preliminary evidence for a mechanism of action for phospholipase A2 activation that represents an alternative to an increase in intracellular calcium concentration. In this fourth submission of this project, previously judged in December 1993 to have been on the cusp of outstanding by this committee, the investigator proposes to continue these studies. Under the first specific aim, they will express PLAP in vitro, purify PLAP in quantity, characterize the purified protein, and obtain amino acid sequences. Under the second specific aim, the investigators will clone PLAP from a human cDNA source. They will evaluate the genetic regulation of PLAP production by inflammatory stimuli and as a new component of this specific aim, they will characterize the activity of PLAP in an animal model of PLAP-induced rheumatoid arthritis.

描述：（改编自申请人的摘要）炎症

项目成果

A phospholipase A2-activating protein (PLAP) stimulates human neutrophil aggregation and release of lysosomal enzymes, superoxide, and eicosanoids.

磷脂酶 A2 激活蛋白 (PLAP) 刺激人中性粒细胞聚集并释放溶酶体酶、超氧化物和类二十烷酸。

• 发表时间: 1989
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Bomalaski,JS;Baker,DG;Brophy,L;Resurreccion,NV;Spilberg,I;Muniain,M;Clark,MA
• 通讯作者: Clark,MA

Yeast mitochondria (Saccharomyces cerevisiae) contain Ca(2+)-independent phospholipase A1 and A2 activities: effect of respiratory state.

酵母线粒体（酿酒酵母）含有独立于 Ca(2) 的磷脂酶 A1 和 A2 活性：呼吸状态的影响。

• 发表时间: 1991
• 期刊: Biochemistry international
• 作者: Yost,RW;Grauvickel,SJ;Cantwell,R;Bomalaski,JS;Hudson,AP
• 通讯作者: Hudson,AP

Identification and isolation of a phospholipase A2 activating protein in human rheumatoid arthritis synovial fluid: induction of eicosanoid synthesis and an inflammatory response in joints injected in vivo.

人类风湿性关节炎滑液中磷脂酶 A2 激活蛋白的鉴定和分离：诱导体内注射的关节中类二十烷酸的合成和炎症反应。

• 发表时间: 1990
• 期刊: The Journal of laboratory and clinical medicine
• 作者: Bomalaski,JS;Fallon,M;Turner,RA;Crooke,ST;Meunier,PC;Clark,MA
• 通讯作者: Clark,MA

Monosodium urate crystals stimulate phospholipase A2 enzyme activities and the synthesis of a phospholipase A2-activating protein.

尿酸钠晶体刺激磷脂酶 A2 酶活性和磷脂酶 A2 激活蛋白的合成。

• 发表时间: 1990
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Bomalaski,JS;Baker,DG;Brophy,LM;Clark,MA
• 通讯作者: Clark,MA

Phospholipase A2-activating protein induces the synthesis of IL-1 and TNF in human monocytes.

磷脂酶 A2 激活蛋白诱导人单核细胞合成 IL-1 和 TNF。

• 发表时间: 1995
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Bomalaski,JS;Ford,T;Hudson,AP;Clark,MA
• 通讯作者: Clark,MA