Dolecki G J, Rogers M, Lefkowith J B
Department of Medicine, Washington University School of Medicine, St. Louis Missouri, USA.
Prostaglandins. 1995 Jun;49(6):397-414. doi: 10.1016/0090-6980(95)00067-k.
Macrophages (M phi s) exhibit variations in their ability to release and metabolize arachidonate (AA) depending on their state of activation, differentiation, and tissue origin. In order to understand these variations on a molecular level, we determined whether differences in AA release and metabolism by murine peritoneal M phi s could be explained in terms of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX) expression. Resident M phi s exhibited greater COX capacity (conversion of exogenous AA to PGE2) but lower phospholipase (PLase) activity (release of endogenous AA) than elicited M phi s. Activation of resident M phi s in vivo with endotoxin increased both their PLase activity and COX capacity. Despite the observed differences in PLase activity, peritoneal M phi s under all conditions expressed similar amounts of cPLA2 mRNA and protein. All M phi s exhibited COX-1 mRNA and protein (i.e., the constitutive isoform of COX), although elicited M phi s exhibited increased mRNA for COX-1 but decreased levels of protein, relative to resident M phi s. Elicited (but not resident) cells also exhibited COX-2 mRNA but not COX-2 protein (i.e., the inducible form of COX). Despite the increased COX capacity of resident cells with in vivo activation, their expression of COX-2 mRNA and protein was equivalent to that of unactivated cells, becoming apparent only after cell adherence in vitro. In sum, there is no simple relationship between the ability of M phi s to release and metabolize AA, and the expression of cPLA2 or COX isoforms. Moreover, adherence appears to be important for the expression of COX-2 by M phi s.
巨噬细胞（M phi s）释放和代谢花生四烯酸（AA）的能力因其激活状态、分化程度和组织来源而异。为了在分子水平上理解这些差异，我们确定了小鼠腹膜巨噬细胞AA释放和代谢的差异是否可以用胞质磷脂酶A2（cPLA2）和环氧化酶（COX）的表达来解释。与诱导性巨噬细胞相比，驻留性巨噬细胞表现出更高的COX活性（将外源性AA转化为PGE2），但磷脂酶（PLase）活性较低（内源性AA的释放）。用内毒素在体内激活驻留性巨噬细胞会增加其PLase活性和COX活性。尽管观察到PLase活性存在差异，但在所有条件下，腹膜巨噬细胞表达的cPLA2 mRNA和蛋白质数量相似。所有巨噬细胞都表现出COX-1 mRNA和蛋白质（即COX的组成型同工型），尽管相对于驻留性巨噬细胞，诱导性巨噬细胞的COX-1 mRNA增加，但蛋白质水平降低。诱导性（而非驻留性）细胞也表现出COX-2 mRNA，但没有COX-2蛋白质（即COX的诱导型）。尽管驻留性细胞在体内激活后COX活性增加，但其COX-2 mRNA和蛋白质的表达与未激活细胞相当，仅在体外细胞贴壁后才变得明显。总之，巨噬细胞释放和代谢AA的能力与cPLA2或COX同工型的表达之间没有简单的关系。此外，贴壁似乎对巨噬细胞COX-2的表达很重要。
