MCP HAHNEMANN SCHOOL OF MEDICINE

描述：（改编自申请人摘要） 许多设置似乎是由介导的和/或放大的 磷脂酶这位调查员和他的同事已经证明了 细胞和滑液中磷脂酶A2酶活性 类风湿性关节炎患者。他们还发现， 其特征在于磷脂酶A2活化蛋白（PLAP），并且具有 证明了这种蛋白质对细胞和磷脂酶的影响 A2.他们已经证明，将PLAP注射到兔子关节中， 导致了一种炎症性关节炎反应， 类风湿关节炎此外，接触外周血 白细胞转化为PLAP导致类花生酸和超氧化物 沿着细胞脱颗粒的产生。他们最近克隆了 并获得了PLAP的cDNA。他们还初步生成了 磷脂酶A2激活作用机制的证据， 代表了细胞内钙增加的替代方案 浓度. 在这个项目的第四次提交中， 1993年，在本委员会尚未完成的最高峰上， 研究者建议继续这些研究。根据第一项 有针对性地在体外表达PLAP，大量纯化PLAP， 对纯化的蛋白质进行表征，并获得氨基酸序列。 根据第二个具体目标，研究人员将克隆PLAP， 人cDNA来源。他们将评估PLAP的遗传调控 通过炎症刺激产生，并作为其新的组成部分， 为了达到特定的目的，他们将表征PLAP在动物中的活性 PLAP诱导的类风湿性关节炎模型。

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.