Holgate S T, Burns G B, Robinson C, Church M K
J Immunol. 1984 Oct;133(4):2138-44.
Proteolytic digestion of human lung tissue dispersed a population of cells (HDLC) containing 1 to 8% mast cells but which were free from bronchial and vascular smooth muscle. Incubation of HDLC with anti-human IgE, which released a net 24.8 + 4.3% of mast cell-derived histamine, stimulated a 14-fold increase in the generation of PGD2, a seven-fold increase in TXB2, and less than a twofold increase in PGF2 alpha, immunoreactive PGE, (i-PGE) and 6-keto-PGF1 alpha. A similar profile of prostanoid release was observed when cells were challenged with epsilon-specific anti-IgE, indicating that the response was specific to the coupling of IgE Fc receptors. The calcium ionophore A23187 also released prostanoids from HDLC in approximately the same proportions as anti-IgE. This stimulus, however, released only 50% as much PGD2 per nanogram histamine than did IgE-dependent activation, thereby showing a fundamental difference in the mechanisms by which the two agents activate mast cells and liberate arachidonic acid for oxidative metabolism. In concentration-response and time course experiments, both secretory stimuli released prostanoids and histamine in parallel. After separation of lung cells by isopyknic centrifugation, challenge with anti-IgE or A23187 released PGD2 only from those fractions containing mast cells, the amount released corresponding closely to both the mast cell concentration and net histamine release. On pooling data from all experiments, the closest correlation was found between release of PGD2 and histamine when cells were stimulated with either anti-IgE (r = 0.813, p less than 0.001) or A23187 (r = 0.763, p less than 0.001), supporting a mast cell origin for PGD2. The release of other prostanoids in fractions not containing mast cells demonstrates that macrophages, monocytes, and lymphocytes have the capacity to generate TXB2, PGF2 alpha, and i-PGE both in the absence and presence of mast cells. Thus, although mast cells are likely to be the major source of PGD2 generated upon IgE-dependent stimulation of HDLC, other cells dispersed from lung tissue have the capacity to generate prostanoids directly after activation of their IgE-Fc receptors and, indirectly after the secretion of mast cell mediators.
人肺组织的蛋白水解消化分散出一群细胞（人肺消化细胞，HDLC），其中含有1%至8%的肥大细胞，但不含支气管和血管平滑肌。用抗人IgE孵育人肺消化细胞，释放出净含量为24.8 + 4.3%的肥大细胞源性组胺，刺激前列腺素D2（PGD2）生成增加14倍，血栓素B2（TXB2）增加7倍，前列腺素F2α（PGF2α）、免疫反应性前列腺素E（i-PGE）和6-酮-前列腺素F1α增加不到2倍。当用ε特异性抗IgE刺激细胞时，观察到类似的前列腺素释放模式，表明该反应对IgE Fc受体的偶联具有特异性。钙离子载体A23187也能使人肺消化细胞释放前列腺素，其比例与抗IgE大致相同。然而，这种刺激每纳克组胺释放的PGD2仅为IgE依赖性激活的50%，从而表明这两种试剂激活肥大细胞并释放花生四烯酸进行氧化代谢的机制存在根本差异。在浓度-反应和时间进程实验中，两种分泌刺激均平行释放前列腺素和组胺。通过等密度离心分离肺细胞后，用抗IgE或A23187刺激仅从含有肥大细胞的那些组分中释放PGD2，释放量与肥大细胞浓度和净组胺释放量密切相关。汇总所有实验的数据后发现，当用抗IgE（r = 0.813，p < 0.001）或A23187（r = 0.763，p < 0.001）刺激细胞时，PGD2释放与组胺释放之间的相关性最为密切，支持PGD2来源于肥大细胞。在不含肥大细胞的组分中其他前列腺素的释放表明，巨噬细胞、单核细胞和淋巴细胞在有或没有肥大细胞的情况下都有能力生成TXB2、PGF2α和i-PGE。因此，尽管肥大细胞可能是人肺消化细胞在IgE依赖性刺激下产生的PGD2的主要来源，但从肺组织分散出的其他细胞在其IgE-Fc受体激活后有能力直接生成前列腺素，在肥大细胞介质分泌后则间接生成。
