Nichols F C, Garrison S W, Davis H W
Department of Periodontology, University of Connecticut School of Dental Medicine, Farmington 06032.
J Leukoc Biol. 1988 Nov;44(5):376-84. doi: 10.1002/jlb.44.5.376.
We investigated the capacity of counterflow-isolated human monocytes to independently synthesize thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) when stimulated with bacterial lipopolysaccharide (LPS). Independent metabolism was confirmed by establishing different specific activities (dpm/ng) of TxB2 and PGE2 released from LPS-treated cells. For metabolites released during the initial 2-hr treatment period, the specific activity of PGE2 was approximately threefold higher than that of TxB2 regardless of labeling with [3H]arachidonic acid (AA) or [14C]AA. Cells that were pulse-labeled for 2 hr with [3H]AA demonstrated a decreasing PGE2 specific activity over 24 hr, whereas the TxB2 specific activity remained unchanged. In contrast, cells continuously exposed to [14C]AA demonstrated an increasing TxB2 specific activity that approached the level of PGE2 by 24 hr. These results suggest the presence of at least 2 cyclooxygenase metabolic compartments in counterflow-isolated monocytes. Although freshly isolated monocytes have been reported to contain variable numbers of adherent platelets, additional experiments demonstrated that counterflow-isolated platelets are not capable of releasing elevated levels of TxB2 or PGE2 when treated with LPS. It is proposed from these findings that at least two subsets of monocytes exist in peripheral blood that can be distinguished on the basis of independent conversion of AA to TxB2 and PGE2.
我们研究了逆流分离的人单核细胞在受到细菌脂多糖(LPS)刺激时独立合成血栓素B2(TxB2)和前列腺素E2(PGE2)的能力。通过确定从LPS处理的细胞中释放的TxB2和PGE2的不同比活性(dpm/ng)来证实独立代谢。对于最初2小时处理期间释放的代谢产物,无论用[3H]花生四烯酸(AA)还是[14C]AA标记,PGE2的比活性均比TxB2高约三倍。用[3H]AA脉冲标记2小时的细胞在24小时内PGE2比活性降低,而TxB2比活性保持不变。相反,持续暴露于[14C]AA的细胞显示TxB2比活性增加,到24小时时接近PGE2的水平。这些结果表明在逆流分离的单核细胞中至少存在2个环氧化酶代谢区室。尽管有报道称新鲜分离的单核细胞含有数量可变的黏附血小板,但额外的实验表明,逆流分离的血小板在用LPS处理时不能释放升高水平的TxB2或PGE2。根据这些发现推测,外周血中至少存在两个单核细胞亚群,可根据AA向TxB2和PGE2的独立转化来区分。