苯并异硒唑酮磺酰胺类化合物的抗炎作用

目的　研究苯并异硒唑酮磺酰胺类化合物A和B抗炎作用。方法　Boyden 小室法测定中性粒细胞趋化;紫外分光光度法测定髓过氧化物酶活性;染色法测定肥大细胞脱颗粒。结果　化合物A和B均可抑制fMLPP诱导的兔外周血中性粒细胞趋化反应;外涂给药均可抑制巴豆油引起的小鼠髓过氧化物酶的升高。在10^-7～10^-5　mol.L^-1浓度下可抑制化合物48/80诱导的肥大细胞脱颗粒,并与浓度呈正相关。结论　苯并异硒唑酮磺酰胺类化合物A和B有明确的抗炎作用。     

银杏内酯B对血小板活化因子刺激的大鼠中性粒细胞功能的影响银杏内酯B对血小板活化因子刺激的大鼠中性粒细胞功能的影响

目的 研究银杏内酯B对血小板活化因子(PAF)刺激的大鼠中性粒细胞粘附、趋化及脱颗粒功能的影响。方法 从大鼠外周血分离中性粒细胞,用MTT比色法、Boyden小室法及β-葡萄糖苷酸酶释放法分别检测PAF诱导的粒细胞粘附、趋化及脱颗粒反应。结果10 μmol·L^-1 银杏内酯B可显著抑制中性粒细胞的粘附反应;1～1 000 nmol·L^-1 可剂量依赖性抑制10 nmol·L^-1 PAF诱发的粒细胞趋化反应,其IC₅₀为4.84 nmol·L^-1; 0.01～10 μmol·L^-1可抑制1 μmol·L^-1 PAF诱发的粒细胞释放β-葡糖苷酸酶,其IC₅₀为3.56 μmol·L^-1。结论银杏内酯B能够抑制PAF刺激的大鼠中性粒细胞粘附、趋化及脱颗粒反应。     

柠檬醛对致敏大鼠腹腔肥大细胞脱颗粒和气道嗜酸粒细胞凋亡的作用

目的:研究柠檬醛对致敏大鼠肥大细胞脱颗粒的影响以及对大鼠气道嗜酸粒细胞凋亡的作用。方法:以卵蛋白致敏制备大鼠哮喘模型。通过大鼠被动肥大细胞脱颗粒,放免法测定肿瘤坏死因子α(TNF-α)和白细胞介素8(IL-8)的含量;密度梯度离心法分离支气管肺泡灌洗液中的嗜酸粒细胞,采用膜联蛋白和碘化丙啶联合标记法测定细胞凋亡,流式细胞仪检测细胞凋亡情况。结果:柠檬醛高、中剂量组肥大细胞脱颗粒数量以及TNF-α和IL-8的含量与模型组相比差异有非常显著意义(P<0.01);柠檬醛高、低剂量组都能明显提高嗜酸粒细胞的凋亡量,与空白对照组相比差异有非常显著意义(P<0.01)。结论:柠檬醛具有抑制肥大细胞脱颗粒作用并且促进嗜酸粒细胞凋亡。     

牛膝多糖对抗原诱导的肥大细胞活化的影响

目的观察牛膝多糖(achyranthes bidentata polysaccha-rides,ABPS)对肥大细胞活化脱颗粒的影响。方法运用大鼠被动皮肤过敏反应(PCA)实验,用比色测定法检测ABPS在体内对肥大细胞(MC)影响;体外实验将ABPS分为高、中、低3个剂量组,然后分别将其加入抗原致敏的RBL-2H3细胞中(大鼠嗜碱性粒细胞白血病细胞,国际公认的MC研究模型细胞),观察ABPS对RBL-2H3细胞脱颗粒的影响。结果ABPS能明显抑制大鼠PCA、RBL-2H3细胞脱颗粒,并能抑制RBL-2H3细胞释放组胺、肿瘤坏死因子α及白细胞介素4;抑制RBL-2H3细胞中Akt和p38的磷酸化。结论ABPS的抗过敏作用与抑制肥大细胞的脱颗粒及炎性物质释放有关;ABPS抑制肥大细胞的活化与抑制Akt和p38的活性相关。     

黄芪注射液对内毒素诱导大鼠肠系膜微循环障碍改善作用的实验研究

目的探讨静脉给予黄芪注射液对内毒素血症肠系膜微循环障碍的改善作用。方法 Wistar大鼠30只为对照组、模型组、治疗组,每组10只。采用静脉注入脂多糖（LPS）（5mg·kg-1·h-1）复制内毒素血症模型,治疗组给予静脉注射黄芪注射液（5ml·kg-1·h-1）,用微循环观察系统每20分钟动态观察细静脉粘附白细胞,细静脉血管壁过氧化物的动态变化。在100min观察结束后,计数肠系膜间质内肥大细胞脱颗粒率。取外周血,用流式细胞仪测定粒细胞粘附分子CD11b和CD18的表达。结果模型组在LPS滴注20min后,黏附于大鼠肠系膜细静脉壁上的白细胞数和管壁过氧化物依存的DHR的荧光强度显著增加,100min时计数肠系膜间质内肥大细胞脱颗粒率显著地增加（P〈0.05）。流式细胞仪测定外周血粒细胞黏附分子CD11b和CD18的表达明显增加（P〈0.05）。治疗组白细胞与肠系膜细静脉的血管壁黏附;细静脉壁过氧化物依存的DHR荧光强度的增加,肠系膜间质内肥大细胞脱颗粒率,外周血粒细胞黏附分子CD11b和CD18的表达明显受到抑制（P〈0.01）。结论黄芪注射液对内毒素血症肠系膜微循环障碍有改善作用。可能其抑制粒细胞黏附分子CD11b和CD18表达及肥大细胞脱颗粒相关。     

鼻炎口服液抗过敏、抗炎作用实验研究

目的：研究鼻炎口服液抗过敏与抗炎作用，为其临床应用提供理论依据。方法：采用抗血清致大鼠同种被动皮肤过敏和大鼠颅骨骨膜肥大细胞脱颗粒、卵蛋白（OA）引起豚鼠鼻黏膜过敏反应与2．4-二硝基氯苯（DNCB）诱发的DTH小鼠迟发性超敏反应，考察鼻炎口服液的抗过敏作用；采用组胺诱发大鼠毛细血管通透性增高、二甲苯致小鼠耳廓肿胀、大鼠棉球肉芽肿及角叉菜胶致大鼠足跖肿胀，考察鼻炎口服液的抗炎作用。结果：鼻炎口服液能显著抑制大鼠同种被动皮肤过敏和豚鼠鼻黏膜过敏反应，阻止大鼠颅骨骨膜肥大细胞脱颗粒，抑制DTH小鼠迟发性超敏反应，大剂量时还可增加小鼠的胸腺指数及脾指数；对组胺诱发大鼠毛细血管通透性增高、二甲苯致小鼠耳廓肿胀、大鼠棉球致肉芽组织增生均有显著的抑制作用，能显著降低大鼠角叉菜胶性足跖肿胀及炎症组织内PGE，含量。结论：鼻炎口服液具有明显的抗过敏和抗炎作用。     

Vam3抗磷酸组胺致豚鼠哮喘作用的研究

我们以往研究表明,天然二苯乙烯低聚体类化合物Vam3,具有确切的抗炎作用。本实验旨在通过研究Vam3的抗哮喘作用,初步探讨yam3抗慢性阻塞性肺疾病（COPD）的机制。观察Vain3对磷酸组胺致豚鼠哮喘模型的影响,将豚鼠随机分成对照组,阳性药组（孟鲁斯特）,大剂量组（50mg）,小剂量组（25mg）,每组8只。观察各组豚鼠气道病理改变,对支气管肺泡灌洗液（BALF）进行总细胞计数,采用ELIsA法检测豚鼠支气管肺泡灌洗液（BALF）及血清中TNFα,IL-4的浓度。研究发现Vam3能够减轻支气管肺泡炎性反应,减少BALF中的炎性细胞总数,抑制肥大细胞脱颗,降低TNFa、IL-4水平。病理结果显示,模型组粘液分泌增多等气道炎症的症状。Vam3给药组及阳性对照组与模型组比较,炎症反应较轻微,对气道炎症有一定的改善作用。表明Vam3通过抑制炎症细胞浸润和炎症细胞因子的生成来发挥抗哮喘作用。拟进一步观察Vam3对气道平滑肌MMP-9表达和气道上皮细胞凋亡以及对气道重塑的影响等,为探讨Vam3抗哮喘作用机理提供实验依据。     

N-(3’,4’,5’-三甲氧基肉桂酰)邻氨基苯甲酸对抗原诱发的离体豚鼠回肠收缩、大鼠肥大细胞脱颗粒及组胺释放的影响

实验证明 N-(3′,4′,5′-三甲氧基肉桂酰)邻氨基苯甲酸(TOA)管内浓度80μg/ml 能明显抑制抗原诱发的主动致敏豚鼠离体回肠收缩。TOA 管内浓度25和50μg/ml 能显著抑制亲同种细胞抗体介导的大鼠肠系膜肥大细胞脱颗粒和腹腔肥大细胞组胺释放。     

黄连素的抗炎作用及其机制

目的探讨黄连素抗炎作用及其机制。方法（采用中性粒细胞趋化法、化学发光法、微酸滴定法和紫外分光光度法等，从细胞和分子水平观察黄连素（berberine，Ber）对中性粒细胞及几种重要炎症介质的影响。结果5×10-5、5×10-4mol·L-1明显抑制趋化因子ZAP（zymosan-activitedplasma）诱导的中性粒细胞趋化;抑制多形核白细胞酵母多糖诱导的化学发光;对白细胞系产生的羟自由基及过氧化氢导致的化学发光亦有显著的抑制作用;明显降低中性粒细胞中磷脂酶A2（PLA2）的活性。在整体实验中，Ber30、60、90mg·kg-1，ig，可明显降低大鼠炎症组织中PGE2的含量。结论Ber的抗炎作用可能与抑制中性粒细胞趋化、产生活性氧的功能，抑制自由基产生，降低PLA2活性，减少炎症组织中PGE2的产生等多因素有关。     

N—（3′，4′，5′—三甲氧基肉桂酰）邻氨基苯甲酸对抗原诱发的离体豚鼠回肠收缩、大鼠肥大细胞脱颗粒及组胺释放的影响

实验证明N－（3′，4′，5′－三甲氧基肉桂酰）邻氨基苯甲酸（TOA）管内浓度80μg/ml能明显抑制抗原诱发的主动致敏豚鼠离体回肠收缩。TOA管内浓度25和50μg/ml能显著抑制亲同种细胞抗体介导的大鼠肠系膜肥大细胞脱颗粒和腹腔肥大细胞组胺释放。     

中药有效成分Vam3对小鼠气道非特异性炎症模型T_H1/T_H2应答的调节作用

本研究的目的是利用气道炎症小鼠模型来探讨中药有效成分Vam3调节气管炎症的免疫平衡的效果。小鼠用伴清蛋白腹膜内致敏,然后气管内发敏。在首次发敏后24h用中药有效成分Vam3进行治疗。用地塞米松治疗组、生理盐水组及不作处理的空白对照组作为对照。中药有效成分Vam3的评价主要是对抗原特异性抗体的产生及产生细胞因子类型的影响。结果显示,与盐水对照组相比,中药有效成分Vam3可有效减少抗原特异性IgE、IL-4、IL-5和IL-13的水平,而IgG2和IFN-γ合成不受抑制。证实其有抗气道炎症和调节TH1/TH2应答类型的作用,可用于气道炎症的治疗。     

Comparative effects of inhibitors of the lipoxygenase enzyme system on leucocyte chemotaxis

The chemotactic response, towards zymosan activated serum (ZAS), of elicited peritoneal exudate leucocytes was assessed in-vitro after treatment with inhibitors of the lipoxygenase enzyme pathway. Leucocytes from both rat and guinea-pig were used. BW755C and benoxaprofen reduced the chemotaxis of mononuclear cells from both species at 10(-4) M. Nordihydroguaiaretic acid (NDGA) at 7.5 X 10(-6) M depressed the chemotaxis of rat mononuclear cells but failed to modify the response of guinea-pig mononuclear cells. NDGA, BW755C and benoxaprofen, at concentrations that inhibit the lipoxygenase enzyme pathway in-vitro, were ineffective in reducing the chemotactic response of rat PMN. All three agents potentiated guinea-pig PMN chemotaxis, to a greater or lesser extent, the most pronounced effect being with NDGA when increased PMN migration was accompanied by an increased detachment of cells from the lower surface of the filters. The effects of these agents on both cellular chemotaxis and adherence are not necessarily related to their inhibitory effects on the lipoxygenase enzyme pathway.     

Pharmacokinetic analysis and tissue distribution of Vam3 in the rat by a validated LC-MS/MS method

Vam3 is a potential pharmacologically active ingredient isolated from Vitis amurensis Rupr. A rapid, simple and sensitive method to determine Vam3 levels in rat plasma and tissue was developed based on LC-MS/MS. Vam3 and an internal standard (IS) were chromatographed on a C18 short column with acetonitrile–0.1% formic acid in water by gradient elution. MS detection was performed by electrospray ionization in negative ion multiple reaction–monitoring modes. This method monitored the transitions m/z 451.0→345.0 and m/z 301.0→164.0 for Vam3 and IS, respectively. The calibration curve was linear over a concentration range of 1.64–1000 ng/mL. The inter-day and intra-day variabilities in precision was less than 12.8%, while the inter-day and intra-day accuracies ranged from –10.60% to 9.08% in plasma and tissue homogenates. This method was applied to investigate the pharmacokinetics and tissue distribution of Vam3 in rats. The results indicated that Vam3 had poor absorption into systemic circulation and extensive tissue distribution after oral administration, and the absolute bioavailability was low (0.79%). Vam3 had a relatively long terminal elimination half-life in lung, and the highest concentration was found in small intestinal tissue. The developed method and the pharmacokinetic data can provide a basis for further studies on the bioactivity of Vam3.KEY WORDS: Vam3, Pharmacokinetics, Tissue distribution, Absolute bioavailability, LC-MS/MS     

Effects of thalidomide on neutrophil respiratory burst, chemotaxis, and transmigration of cytokine- and endotoxin-activated endothelium

Vascular endothelium activated by endotoxin and cytokines plays an important role in organ inflammation and blood leukocyte recruitment. Neutrophils, which are a homogeneous population of effector cells, are rapidly attracted in large numbers to sites of inflammation where they form an early response to infection or injury. Excessive production of various interleukins, TNF, arachidonic acid metabolites, and other substances by neutrophils and macrophages results in systemic endothelial cell injury, a fundamental problem. In the present study, we investigated in vitro the effects of thalidomide (THD) on activation of endothelial cells for enhanced transmigration of neutrophils by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF), and interleukin-1 (IL-1). Modulation of endotoxin- and cytokine-induced neutrophil chemotaxis and respiratory burst by THD were also studied. Treatment of HUVEC with THD in combination with LPS, TNF, and IL-1, respectively, antagonized LPS-activated transmigration of neutrophils but stimulated the effects of TNF and IL-1. All of the agents used – THD, LPS, TNF, and IL-1 – inhibited neutrophil chemotaxis. Addition of THD to the neutrophils had no effect on LPS-inhibited chemotaxis whereas the TNF- and IL-1-induced chemotaxis was modulated in a bimodal manner. However, THD failed to influence neutrophil respiratory burst activity. Results demonstrate that THD differentially affects mediator-induced activation of HUVEC and neutrophils. Received: 1 April 1997 / Accepted: 4 July 1997     

Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes

Objectives A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro. Methods The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol‐based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique. Key findings Compounds 6 , 17 , 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7 , 17 , 18 , 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration. Conclusions The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.     

Vam3, a resveratrol dimer,inhibits cigarette smoke- induced cell apoptosis in lungs by improving mitochondrial function

Aim： To investigate the effects of Vam3 （a resveratrol dimer extracted from Vitis amurensis Rupr） on cigarette smoke （CS）-induced cell apoptosis in lungs in vitro and in vivo and the underlying mechanisms of action.
Methods： Human bronchial epithelial cell line BEAS-2B was exposed to cigarette smoke condensate （CSC, 300 mg/L）, and cell apoptosis was determined using flow cytometry and Hoechst staining. Mitochondrial membrane potential was examined with TMRE staining. ROS and ceramide levels were detected with DCFH-DA fluorescence and HPLC-MS/MS, respectively. Cytochrome c release was detected using immunofluorescence. Caspase-9 and neutral sphingomyelinase 2 expression was measured with Western blotting. The breast carcinoma cell line MCF7 stably expressing GFP-tagged Bax was used to elucidate the role of mitochondria in CS-induced apoptosis. For in vivo study, male mice were exposed to CS for 5 min twice a day for 4 weeks. The mice were orally administered Vam3 （50 mg·kg^-1·d^-1） or resveratrol （30 mg·kg^-1·d^-1） each day 1 h before the first CS exposure.
Results： Pretreatment of BEAS-2B cells with Vam3 （5 μmol/L） or resveratrol （5 μmol/L） significantly suppressed CSC-induced apoptosis, and prevented CSC-induced Bax level increase in the mitochondria, mitochondrial membrane potential loss, cytochrome c release and caspase-9 activation. Furthermore, pretreatment of BEAS-2B cells with Vam3 or resveratrol significantly suppressed CSC-stimulated intracellular ceramide production, and CSC-induced upregulation of neutral sphingomyelinase 2, the enzyme responsible for ceramide production in bronchial epithelial cells. Similar results were obtained in C6-pyridinium ceramide-induced apoptosis of GFP-Bax-stable MCF7 cells in vitro, and in the lungs of CS-exposed mice that were treated with oral administration of Vam3 or resveratrol.
Conclusion： Vam3 protects bronchial epithelial cells from CS-induced apoptosis in vitro and in vivo by preventing mitochondrial dysfunction.     

Morphine inhibits human microglial cell production of, and migration towards, RANTES

The beta-chemokine RANTES has recently been implicated in the neuropathogenesis of the human immunodeficiency virus. Based upon previous studies of the effects of morphine on microglial cell production of cytokines and chemotaxis towards the activated complement component C5a, we tested the hypothesis that this opiate would alter the production of and migration towards RANTES by human microglia. Treatment of highly purified microglial cell cultures with morphine (10(-8)-10(-6) M) potently inhibited RANTES production by lipopolysaccharide- and interleukin-1beta-stimulated cells. Using a chemotaxis chamber to assess directed migration towards RANTES, treatment of microglial cells with morphine (10(-10)-10(-6) M) was found to suppress chemotaxis. The inhibitory effects of morphine on RANTES production and on chemotaxis were blocked by naloxone and beta-funaltrexamine, indicating that morphine mediated its suppressive effects via activation of microglial p-opioid receptors. Morphine's inhibitory effect on chemotaxis did not appear to be associated with an alteration in RANTES-induced [Ca2+]i mobilization. While the clinical significance of these in-vitro findings is unknown, they suggest that mu-opioid receptor agonists could alter certain neurodegenerative and inflammatory processes within the brain.     

Inhibitory effects of C4a on chemoattractant and secretagogue functions of the other anaphylatoxins via Gi protein-adenylyl cyclase inhibition pathway in mast cells

A recombinant complement anaphylatoxin, C4a, inhibited chemotaxis, respiratory burst and histamine release in mast cell-like HMC-1 cells that were treated with recombinant C5a anaphylatoxin. C4a also inhibited histamine release from HMC-1 cells that were induced by recombinant C3a. The inhibition of C5a- and C3a-induced leukocyte reactions by C4a was recapitulated in peripheral blood CD133(+) cell-derived differentiated mast cells. In HMC-1 cells, C4a inhibited cytoplasmic Ca(2+) influx, an event that precedes anaphylatoxin-induced chemotactic and secretary responses. A conditioned medium of HMC-1 cells after shortly treated with C4a also inhibited the anaphylatoxin-induced Ca(2+) influx even after removal of C4a, indicating that the effect of C4a is to liberate an autocrine inhibitor from the mast cells. The inhibitor secretion by C4a was prevented with pertussis toxin or with a phosphodiesterase inhibitor. Conversely, an adenylyl cyclase inhibitor reproduced the effect of C4a. C4a decreased the intracellular cyclic AMP concentration of HMC-1 cells, indicating that C4a elicited the Gi protein-adenylyl cyclase inhibition pathway. Neither C4a nor the conditioned medium, however, inhibited Ca(2+) influx and respiratory burst in C5a- or C3a-stimulated peripheral neutrophils, suggesting that these cells lack this inhibitory system. Additionally, in HMC-1 cells, C4a did not inhibit Ca(2+)-independent, Leu72Gln-C5a-stimulated chemotactic response. In agreement with this finding, C4a treatment inhibited ERK1/2 phosphorylation in HMC-1 cells stimulated with other anaphylatoxins but did not inhibit p38MAPK phosphorylation in cells stimulated with Leu72Gln-C5a. Taken together, these findings suggest that the autocrine inhibitory effect elicited by C4a is attributed to interruption of Ca(2+)-dependent intracellular signaling pathway.     

Role of cyclic GMP on inhibition by nitric oxide donors of human eosinophil chemotaxis in vitro

1. This study was designed to investigate the effects of the nitric oxide (NO) donors sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP) on N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP, 1 x 10(-7) M)-induced human eosinophil chemotaxis, cyclic guanosine-3',5'-monophosphate (cGMP) levels, protein nitration and cytotoxicity. 2. Human eosinophils were exposed to SNP, SIN-1 and SNAP (0.001-1.0 mM) for either short (10 min) or prolonged (90 min) time periods. Exposition of eosinophils with these NO donors significantly inhibited the eosinophil chemotaxis irrespective of whether cells were exposed to these agents for 10 or 90 min. No marked differences were detected among them regarding the profile of chemotaxis inhibition. 3. Exposition of eosinophils to SNP, SIN-1 and SNAP (0.001-1.0 mM) markedly elevated the cGMP levels above basal levels, but the 90-min exposition resulted in significantly higher levels compared with the 10-min protocols (5.3+/-0.6 and 2.6+/-0.2 nM 1.5 x 10(6) cells(-1), respectively). The cGMP levels achieved with SNAP were greater than SNP and SIN-1. 4. The NO donors did not induce cell toxicity in any experimental condition used. Additionally, eosinophils exposed to SNP, SIN-1 and SNAP (1.0 mM each) either for 10 or 90 min did not show any tyrosine nitration in conditions where a strong nitration of bovine serum albumin was observed. 5. Our findings show that inhibitory effects of fMLP-induced human eosinophil chemotaxis by NO donors at short or prolonged exposition time were accompanied by significant elevations of cGMP levels. However, additional elevations of cGMP levels do not change the functional profile (chemotaxis inhibition) of stimulated eosinophils.     

Inhibition of neutrophil and eosinophil induced chemotaxis by nedocromil sodium and sodium cromoglycate.

1. Neutrophils and eosinophils infiltrate the airways in association with the allergen-induced late phase asthmatic reaction. Mobilization of these cells takes place via lipid-like and protein-like chemotactic factors. In this study platelet-activating factor (PAF), leukotriene B4 (LTB4), zymosan-activated serum (ZAS) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as illustrative examples of both groups. Chemotaxis was studied in human neutrophils and eosinophils. The inhibitory effects of nedocromil sodium and sodium cromoglycate were evaluated. 2. All chemotactic factors tested attracted neutrophils with the following rank order of activity: ZAS greater than PAF identical to FMLP identical to LTB4. Eosinophils were only mobilized by PAF, LTB4 and ZAS with the following rank order of activity: ZAS greater than PAF greater than LTB4. 3. Nedocromil sodium and sodium cromoglycate were equally active as the PAF antagonist BN 52021 in inhibiting the PAF-induced chemotaxis of neutrophils (IC50 approximately 10(-8) M). Both drugs were also equally active in inhibiting the chemotaxis of neutrophils induced by ZAS (IC50 approximately 10(-7)-10(-6) M), FMLP (IC50 approximately 10(-7) M) and LTB4 (IC50 approximately 10(-6) M). 4. Nedocromil sodium significantly inhibited the chemotaxis of eosinophils induced by PAF (IC50 approximately 10(-6) M) and LTB4 (IC50 approximately 10(-7) M). The inhibitory potency of BN 52021 was similar to that of nedocromil sodium on the PAF-induced chemotaxis of eosinophils. Sodium cromoglycate was incapable of eliciting significant inhibition of these chemotactic responses. However, sodium cromoglycate significantly inhibited the chemotaxis of eosinophils induced by ZAS (IC50 approximately 10(-7) M), whereas nedocromil sodium was ineffective.