几种抗痨方药对结核感染中固有免疫作用靶标的研究

目的:探究传统抗痨方药抗结核感染的可能作用靶标。方法:用沙参麦冬汤、百合固金汤、人参蛤蚧散含药血清作用U937细胞株24小时后,分别采用RT-PCR法和流式细胞术检测巨噬细胞表面CR1、CR3、CD14、CD43、TLR2及TLR4 mRNA和蛋白的表达。再以BCG作用于经含药血清干预24小时后的U937细胞株,检测细胞的吞噬杀菌能力。ELISA法检测各组细胞IL-10、IL-12,生化方法检测iNOS的活力。结果:沙参麦冬汤、百合固金汤、人参蛤蚧散含药血清在mRNA和蛋白水平上对巨噬细胞表面模式识别受体的表达均产生一定影响。并可提高巨噬细胞的吞噬百分率、吞噬指数(P0.05)。且不同程度影响IL-10、IL-12等的产生。但对iNOS活力均无显著影响。结论:沙参麦冬汤、百合固金汤、人参蛤蚧散含药血清可在体外影响巨噬细胞表面不同类型的模式识别受体的产生,这可能成为抗结核杆菌感染的药理作用的分子基础;但属滋阴方药的沙参麦冬汤、百合固金汤,与属补气方药人参蛤蚧散对巨噬细胞的影响具有明显不同。     

紫杉醇对骨髓细胞体外诱导分化的巨噬细胞影响

目的:研究紫杉醇对小鼠骨髓分化巨噬细胞的直接影响。方法:常规方法无菌制备BALB/c小鼠骨髓细胞,用含M-CSF的RPMI1640培养液培养7d,同时加入不同浓度紫杉醇,通过流式细胞术对骨髓单核细胞分化的巨噬细胞的表型分子、吞噬功能进行测定,采用迟发型过敏反应(DTH)方法检测巨噬细胞免疫原性。结果:紫杉醇明显降低骨髓单核细胞分化成巨噬细胞的数量;F4/80 巨噬细胞表面分子CD80、CD14表达升高,而I-Ad表达降低;紫杉醇提高分化的巨噬细胞吞噬鸡红细胞的能力;但使其免疫原性降低。结论:紫杉醇能使骨髓单核细胞分化的巨噬细胞细胞吞噬能力提高,但其免疫原性下降,提示紫杉醇可能具有调节巨噬细胞免疫功能的作用。     

连翘提取物对小鼠腹腔巨噬细胞体外吞噬和NO释放的影响

目的:分析连翘(FS)对小鼠腹腔巨噬细胞的体外吞噬和体外NO释放的影响.方法:无菌收集小鼠腹腔巨噬细胞和羧基荧光素乙酰乙酸琥珀酰亚胺酯(CFDA-SE)标记大肠杆菌DH5α,短期培养3 h后流式细胞术(FCM)分析FS对腹腔巨噬细胞体外吞噬的影响.用LPS体外刺激活化腹腔巨噬细胞,Griess Reagent试剂盒检测并分析FS对巨噬细胞体外释放NO的影响.结果:FCM分析显示,终浓度为40、80、160 mg/L的FS对小鼠腹腔巨噬细胞体外吞噬具有明显的促进作用(P<0.05).不同终质量浓度的FS对LPS诱导小鼠腹腔巨噬细胞体外NO的释放均有抑制作用(P<0.05).结论:FS可以促进小鼠腹腔巨噬细胞的体外吞噬和抑制NO体外的释放.     

漆黄素对巨噬细胞和T淋巴细胞的免疫调节作用

目的探讨漆黄素(Fisetin,FIS)对小鼠巨噬细胞吞噬功能、NO的释放及对T淋巴细胞体外活化、增殖的影响。方法无菌制备小鼠巨噬细胞悬液及淋巴细胞悬液;荧光微球结合流式细胞术(FCM)分析FIS对巨噬细胞吞噬作用的影响;Griess试剂盒检测巨噬细胞NO的释放;双色荧光抗体染色结合FCM,检测CD3+T细胞CD69的表达水平;CFSE标记技术检测T细胞增殖的情况。结果 2.5μmol/L,5μmol/L,10μmol/LFIS均能明显抑制巨噬细胞的吞噬微球的能力;FIS能抑制LPS和IFN-γ刺激的巨噬细胞的NO的产生(P<0.05);FIS对ConA刺激的T细胞表达CD69有抑制作用,并能有效抑制ConA诱导的T细胞增殖(P<0.01),且均呈剂量依赖性。结论 FIS能显著抑制小鼠腹腔巨噬细胞的吞噬能力和分泌NO的能力,并能够抑制T细胞的活化和增殖,有望发展成为一种新的免疫抑制药物。     

HMGB1对小鼠腹腔巨噬细胞吞噬和I-A/E表达的影响

目的:探讨HMGB1对巨噬细胞免疫功能的影响.方法:梯度浓度HMGB1处理小鼠腹腔巨噬细胞, 或将小鼠随机分为生理盐水对照、 24 h和48 h高与低剂量HMGB1注射组, 腹腔注射0.2 μg或20 μg HMGB1, 或生理盐水.检测巨噬细胞吞噬功能和I-A/E表达.结果:10 μg/L HMGB1刺激6～12 h, 巨噬细胞吞噬功能较其他剂量组明显增强(P<0.05或P<0.01).HMGB1对培养巨噬细胞I-A/-E表达无影响.高剂量HMGB1攻击小鼠24 h, 其腹腔巨噬细胞吞噬能力明显降低(P<0.05); 低剂量HMGB1攻击48 h, 巨噬细胞I-A/-E表达明显上调(P<0.05或P<0.01).结论:高剂量HMGB1抑制巨噬细胞吞噬功能, 低剂量HMGB1增强巨噬细胞免疫功能.     

猪苓及猪苓多糖对膀胱癌模型大鼠腹腔巨噬细胞吞噬和表面免疫相关分子表达的影响

目的:观察猪苓及猪苓多糖(PPS)对BBN加糖精诱导的膀胱癌大鼠腹腔巨噬细胞的吞噬功能、体外NO释放及共刺激分子和表面分子表达的影响。方法:实验分为空白对照组、模型组、PPS组和猪苓高中低剂量共6组。用流式细胞术检测膀胱癌大鼠腹腔巨噬细胞的荧光微球吞噬率、TLR4/CD14、CD86、CD40的表达。Griess试剂盒检测并分析猪苓及PPS对腹腔巨噬细胞体外NO释放的影响。结果:PPS组与模型组比较,PPS显著促进巨噬细胞吞噬率的增加、NO释放的比值均降低、巨噬细胞表面分子TLR4/CD14、CD86、CD40的表达均显著升高(P<0.05)。不同浓度猪苓组与模型组比较巨噬细胞吞噬率增加、NO释放的比值均降低(P<0.05),巨噬细胞表面分子CD86表达增加。低浓度猪苓组巨噬细胞CD40表达百分率显著升高(P<0.05);但TLR4/CD14的表达无明显变化;中、高剂量猪苓组TLR4/CD14的表达百分率与模型组比较则降低(P<0.05),CD40的表达无统计学差异。结论:PPS可显著促进膀胱癌大鼠腹腔巨噬细胞的吞噬功能和表面免疫相关分子的表达,但猪苓组对巨噬细胞功能的影响因剂量不同而表现出不同结果,可能与猪苓诸多成分同时作用或各成分作用的靶点不同有关。     

用酶解法制备壳寡糖及其对机体免疫功能的调节作用

目的:研究本课题组酶解制备的主要含3-7聚合度壳寡糖(COS)对机体免疫功能的调节作用。方法:利用本课题组分离的高活性壳聚糖酶通过酶水解法制备壳寡糖,HPLC法对壳寡糖的成分进行鉴定,并用异硫氰酸荧光素(FITC)将壳寡糖进行荧光标记得到FITC-COS,研究小鼠腹腔巨噬细胞对壳寡糖的吞噬作用及其与Toll样受体4(TLR4)的关系,进一步研究了不同浓度壳寡糖对小鼠腹腔巨噬细胞的增殖,吞噬中性红能力及分泌TNF-α能力的影响,并对小鼠灌胃不同剂量的壳寡糖,研究了壳寡糖对小鼠血清IgG和IgM含量及小鼠胸腺、脾脏指数的影响。结果:HPLC分析结果显示壳聚糖酶水解法制备的COS主要为3-7单糖聚合度的寡糖。将FITC-COS作用于小鼠腹腔巨噬细胞不同时间后,荧光显微镜观察结果表明巨噬细胞能够吞噬COS,随着时间的延长吞噬COS的量增加,TLR4单克隆抗体预处理巨噬细胞1小时后再加入FITC-COS,巨噬细胞对COS的吞噬作用几乎完全被抑制。COS被巨噬细胞吞噬后可显著增强巨噬细胞的吞噬功能,刺激巨噬细胞分泌TNF-α。体内研究结果表明小鼠灌胃COS能够显著增加小鼠的脾脏指数,增加血清中IgG的含量,对胸腺指数和血清中IgM的含量没有显著影响。结论:壳寡糖(3-7聚合度)能够被巨噬细胞吞噬,进而激活巨噬细胞,具有较好的体外、体内免疫调节功能,壳寡糖对巨噬细胞的激活是通过细胞表面TLR4受体介导的。     

野生型p53基因导入对U937细胞分化和清道夫受体CD36表达的影响

目的 :单核细胞粘附血管内膜 ,向内膜下迁移、分化成为巨噬细胞 ,巨噬细胞吞噬大量氧化型低密度脂蛋白 (ox -LDL)形成泡沫细胞是动脉粥样硬化斑块形成和发展的重要步骤。CD36属于B族清道夫受体 (classBscavengerreceptor) ,是一种功能多样的细胞表面受体 ,ox -LDL孵育单核细胞系U937细胞形成泡沫化细胞过程中有CD36和p5 3基因表达增高 ,巨噬细胞对ox -LDL的吞噬有 4 0 %是由CD36介导。研究单核细胞向巨噬细胞分化和CD36的表达调控机制 ,对于防止动脉粥样硬化的发生与发展具有重要意义。方法 :①U937细胞培养及同步化处理 :人髓系白…     

约氏疟原虫感染小鼠的巨噬细胞表面吞噬相关分子的研究

为探讨致死型约氏疟原虫(Plasmodium yoelii 17XL)感染抵抗型DBA/2小鼠的脾巨噬细胞发挥吞噬功能的作用机制,本试验利用Giemsa薄血膜染色,光学显微镜计数红细胞感染率,观察巨噬细胞的吞噬功能;采用酶联免疫吸附法(ELISA)检测小鼠血清中抗P.y.17XL特异性IgG抗体水平;采用流式细胞技术(FACS)动态检测脾巨噬细胞表面膜分子CD36、CD64表达水平。结果表明,DBA/2小鼠红细胞感染率于感染后第7天高达31.87%,约第15天自愈;感染小鼠脾巨噬细胞吞噬能力于感染后第5天开始增强,至第10天吞噬率高达95%,随后维持于高水平;巨噬细胞表面分子CD36于感染后第3天开始升高,至第10天达到峰值;CD64表达水平于感染后第5天开始升高,随后持续维持于高水平;小鼠血清中抗P.y.17XL特异性IgG抗体水平在感染后第10天开始出现有意义的升高。结果显示,在P.y.17XL感染过程中,巨噬细胞通过表面分子CD36和CD64分别介导的非调理性和调理性吞噬方式杀伤疟原虫,提示巨噬细胞是DBA/2小鼠发挥抗疟保护性免疫的重要效应细胞。     

槲皮素对ox-LDL所致的小鼠巨噬细胞脂质蓄积和过氧化的影响

 目的：研究槲皮素(quercetin,QUE)预处理对氧化低密度脂蛋白 (oxidized low-density lipoprotein,ox-LDL)所致小鼠巨噬细胞脂质蓄积和过氧化的影响,并探讨可能的分子机制。方法：体外培养小鼠RAW264.7巨噬细胞,给予20、40和80 μmol/L QUE预处理30 min,再加入ox-LDL (100 mg/L)继续培养24 h。采用油红O染色检测细胞内脂质蓄积,测定培养液乳酸脱氢酶(lactic dehydrogenase,LDH)、丙二醛(malondialdehyde,MDA)和细胞内活性氧(reactive oxygen species,ROS)水平,以评价细胞膜完整性和脂质过氧化程度。分别采用real-time PCR和免疫印迹技术检测清道夫受体CD36 mRNA和蛋白表达变化。结果：QUE (20,40和80 μmol/L)预处理显著抑制ox-LDL所诱导的巨噬细胞内脂质蓄积和泡沫细胞形成,且呈浓度依赖性。ox-LDL组细胞LDH释放增加,而QUE预处理则显著抑制ox-LDL的上述细胞毒性。与ox-LDL组比较,QUE预处理组细胞内ROS含量和培养液中MDA水平明显降低。另外QUE预处理在mRNA和蛋白水平均明显抑制ox-LDL所诱导的CD36表达上调。结论: QUE可减轻ox-LDL所诱导的小鼠巨噬细胞脂质蓄积和过氧化,其机制可能部分是通过下调CD36表达实现的。     

不同剂量加味保元汤对束缚应激小鼠非特异性免疫功能的影响

目的 :研究不同剂量加味保元汤对束缚应激小鼠非特异性免疫功能的影响。方法 :80只小鼠随机等分为加味保元汤 5g/kg体重、 10g/kg体重、15g/kg体重和应激组 ,用巨噬细胞体内吞噬法 ,测其吞噬率及吞噬指数。结果 :吞噬指数 :10g/kg体重组明显高于 15g/kg体重组 (P <0 0 5 ) ,10g/kg体重组与 5g/kg体重组比较虽P >0 0 5 ,但均值高于 5g/kg体重组 ;吞噬率 :10g/kg体重组最高。结论 :10g/kg体重剂量加味保元汤对束缚应激小鼠非特异性免疫功能保护作用效果最佳。     

Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate

BACKGROUND: Many different types of phthalate ester are used as plasticizers and are thus found in the air. There have been several studies that suggest an association between allergies and phthalate esters. We previously found that di-butyl phthalate (DBP) has an adjuvant effect in a mouse contact hypersensitivity model, in which fluorescein isothiocyanate (FITC) is involved as an immunogenic hapten. OBJECTIVE: We examined whether other phthalate esters enhance the process of sensitization to FITC by facilitating the trafficking of FITC-presenting dendritic cells or macrophages from skin sites to draining lymph nodes. METHODS: Mice were epicutaneously sensitized with FITC dissolved in acetone containing a phthalate ester. Sensitization was evaluated as ear swelling after a challenge with FITC. Draining lymph node cells obtained 24 h after skin sensitization were examined for FITC fluorescence by means of flow cytometry. FITC-positive cells were characterized with anti-CD11c and anti-CD11b by three-colour flow cytometry. RESULTS: When mice were sensitized with FITC in acetone containing DBP or di-n-propyl phthalate (DPP), strong enhancement of the ear-swelling response was observed. Di-methyl phthalate (DMP) and di-ethyl phthalate (DEP) were less effective but produced some enhancement. Consistent enhancement was not observed with di-(2-ethylhexyl) phthalate or di-isononyl phthalate. Upon sensitization in the presence of DBP or DPP, the number of FITC-positive dendritic cells (total CD11c+ as well as CD11c+/CD11b+) was increased in draining lymph nodes. As to the other four phthalate esters, there was no significant increase in the FITC-positive cell number in the draining lymph nodes. CONCLUSION: During the process of sensitization to FITC, DBP, and DPP exert strong adjuvant effects that are associated with enhancement of trafficking of antigen-presenting dendritic cells from the skin to draining lymph nodes.     

Immunomodulation Due to Coexposure to Styrene and Dioctyl Phthalate in Mice

Pathomorphological and immunological alterations caused by a mixture of styrene and dioctyl phthalate were studied in albino mice following oral administration of 0.02, 0.03, 0.05±LD50 of the mixture. The chemicals were mixed together proportionate to their respective LD50 values and fed in ground nut oil, 5d/wk for 4 weeks. Histological examination of spleen revealed considerable depletion of cellular population of lymphoid follicles which corresponded to the dose dependent decrease in splenic mononuclear cell population count. The thymic lobules revealed slight atrophy but accompanied by a significant increase in thymocyte population. Correspondingly few significant histological changes were observed in mesenteric and peripheral lymph nodes. The treatment caused impairment of primary humoral immune response to SRBC (IgM) but there was a significant increase in response of splenocytes to B-cell mitogen LPS. There was a suppression of cutaneous delayed type hypersensitivity and increase in splenic lymphocyte response to T-cell mitogen PHA. Simultaneously, indirect immunity represented by decreased phagocytosis and enhanced metabolic function of reducing NBT by peritoneal exudate cells was observed. The in vitro exposure of vero cells to the mixture caused dose dependent protective effect. The results of present study indicate that subchronic exposure to low doses of mixture of styrene and dioctyl phthalate under certain conditions may modulate some of the immune functions as compared to exposure to either chemicals alone.     

Effects of a glyconutrient on macrophage functions

Previous studies have shown that mannosylated bovine serum albumin (mBSA) enhances the respiratory burst (RB), phagocytosis, and killing of Candida albicans and Escherichia coli by resident murine peritoneal macrophages (Mphi). Upregulation of the above Mphi functions was associated with the binding of mBSA to the macrophage mannose receptor. The present study was done to determine if certain glyconutrients could stimulate Mphi functions in a similar manner. Resident peritoneal murine Mphi collected from C57BL/6 mice were exposed to the glyconutrients for 10 and 60 min. The RB was measured using chemiluminescence. Both phagocytosis and killing were measured after incubation with each of the following microorganisms: Candida albicans, Escherichia coli and Staphylococcus aureus. The percent phagocytosis and killing were determined using fluorescence microscopy. Results indicated that certain glyconutrients, caused a dose and time dependent effect on Mphi-induced killing of all three microorganisms.     

Dependence of macrophage phagocytic efficacy on antibody concentration

Macrophages ingest the fungus Cryptococcus neoformans only in the presence of opsonins, and this provides a remarkably clean system for the detailed analysis of phagocytosis. This system is also unusual in that antibody-mediated phagocytosis involves ingestion through both Fc and complement receptors in the absence of complement. Mathematical modeling was used to analyze and explain the experimental data that the macrophage phagocytic index increased with increasing doses of antibody despite saturating concentrations and declined at high concentrations. A model was developed that explains the increase in phagocytic index with increasing antibody doses, differentiates among the contributions from Fc and complement receptors, and provides a tool for estimating antibody concentrations that optimize efficacy of phagocytosis. Experimental results and model calculations revealed that blocking of Fc receptors by excess antibody caused a reduction in phagocytic index but increased phagocytosis through complement receptors rapidly compensated for this effect. At high antibody concentrations, a further reduction in phagocytic index was caused by interference with complement receptor ingestion as a consequence of saturation of the fungal capsule. The ability of our model to predict the antibody dose dependence of the macrophage phagocytic efficacy for C. neoformans strongly suggest that the major variables that determine the efficacy of this process have been identified. The model predicts that the affinity constant of the opsonic antibody for the Fc receptor and the association-dissociation constant of antibody from the microbial antigen are critical parameters determining the efficacy of phagocytosis.     

Corynebacterium parvum can Reverse the Depression of Macrophage Hydrogen Peroxide Production Caused by Erythrocyte Phagocytosis

Our previous studies have shown that the phagocytosis of IgG-coated erythrocytes (EIgG) in vivo increases the mortality rate with bacterial infection, and EIgG phagocytosis in vitro depresses phorbol myristate acetate (PMA)-triggered H₂O₂ production. The present study was undertaken to determine if the depression of H₂O₂ production caused by EIgG phagocytosis could be reversed by exposing macrophages to priming agents. Macrophages exposed to 100 μg/ml of C. parvum, it's pyridine-soluble extract (PE), or the pyridine extract residue (PER) for 1 hr showed an enhanced production of H₂O₂ in response to PMA triggering. The priming effect of C. parvum, PE, and PER lasted for 3-6 hr. 18 hr after exposure to C parvum or PER, PMA-triggered H₂O₂ production was depressed, however PE did not have this effect. The priming effect of C parvum was not prevented by cycloheximide. EIgG phagocytosis caused a dose dependent depression of PMA-triggered H₂O₂ production. When macrophages were exposed to C. parvum, PE, or PER following EIgG phagocytosis, the priming of PMA-triggered H₂O₂ production was reduced but H₂O₂ production was maintained at levels equal to or greater than that of control macrophages. These results show that phagocytosis did not prevent the action of priming agents on macrophage respiratory burst capacity, and suggests that such agents may preserve macrophage bactericidal function following phagocytosis.     

两型TNF-α对单核细胞系U937细胞功能的影响

目的：比较两型TNF—α对单核细胞系U937细胞功能的影响，以探讨跨膜型TNF—α在炎症中的作用。方法：通过吞噬、RT-PCR、Western blot及FACS等方法，比较两型TNF—α对U937细胞生物学功能(包括吞噬、细胞因子mRNA、胞质IκB—α及ICAM—1表达等)的影响。结果：分泌型TNF—α可明显促进U937细胞吞噬功能，使TNF—α、IL—1β及IL—8 mRNA积累增加，促进胞质IκB—α降解及提高黏附分子ICAM—1的表达；而跨膜型TNF—α对上述U937细胞的生物学功能则无明显影响：当二者联用时，跨膜型TNF—α与分泌型TNF—α亦无协同作用。结论：分泌型TNF—α对U937细胞具有明显地激活作用；而跨膜型TNF—α则无影响，提示两型TNF—α在炎症过程中的作用不同。     

Evaluation of the modulatory effects of in vivo antibiotics on phagocytosis in mice using various methods

The influence of cefoxitin and cefotaxim on phagocytosis in vitro and intracellular microbicidal activity of peritoneal macrophages and granulocytes was examined. In addition, the influence of these antibiotics on the elimination rate of Candida was controlled 4 and 24 hours after intraperitoneal injection. The two antibiotics were shown to have no influence on phagocytosis of Candida. Microbicidal activity was inhibited only by cefoxitin. This result is consistent with the reduction of metabolic activity of phagocytes caused by cefoxitin but not cefotaxim, in vivo as well as in vitro. Both antibiotics induce a reduction of Candida cells recovered 4 hours after intraperitoneal injection. However, the effect of cefotaxim was significantly more pronounced than that of cefoxitin. 24 hours after infection, the result was comparable but the number of Candida cells recovered in the spleen was higher with cefoxitin than with cefotaxim. The clinical bearing of these results remains to be discussed.     

Effect of Trace Metals on Phagocytosis by Alveolar Macrophages

Experiments were performed to measure the effect of trace metals on a vital function of the alveolar macrophage (AM), phagocytosis. Since certain trace metals were found to reduce the viability of AMs, a technique was developed to permit examination of live cells only for phagocytosis. Evidence is presented that Ni(2+) selectively altered the phagocytic activity of AMs at concentrations lower than those which caused cell death. It is further shown that a level of VO(3) (-) that caused extensive lysis and death did not reduce phagocytosis in surviving cells. The effects of Cd(2+), Cr(3+), and Mn(2+) on AMs were also examined.     

Inhibition of alveolar macrophage spreading and phagocytosis by cotton bract tannin. A potential mechanism in the pathogenesis of byssinosis.

One of the major host-defense functions of alveolar macrophages is the phagocytosis and clearance of inhaled particles deposited in the lower airways and alveolar spaces. Recent studies have indicated that the condensed tannins present in cotton mill dust stimulate the secretion of neutrophil chemotactic factor and arachidonic acid from resident rabbit alveolar macrophages and that these responses may contribute to the acute pulmonary inflammatory reaction associated with byssinosis. To characterize further the effect of tannin on macrophage function, the ability of tannin to modulate alveolar macrophage spreading and phagocytosis in vitro was examined. Tannin caused a dose-dependent inhibition of alveolar macrophage spreading with nearly complete inhibition occurring at concentrations of 12.5 micrograms/ml. This inhibitory effect of tannin was not reversed with removal of tannin. Furthermore addition of tannin to previously spread macrophages actively caused the macrophages to round up. Examination of the structure of alveolar macrophages exposed to tannin by scanning and transmission electron microscopy revealed blebs on the surface of the cells and the loss of most of the cellular organelle structure, as compared to control macrophages. Tannin also modulated the ability of the alveolar macrophages to phagocytize unopsonized latex microspheres. The effect of tannin was biphasic. At the lowest concentration examined (3 micrograms/ml), tannin significantly enhanced phagocytosis of the latex microspheres. However, as the concentration was increased, phagocytosis decreased almost exponentially until at 50 micrograms/ml phagocytosis was significantly inhibited compared to control macrophages. These data indicate that tannin present in inhaled cotton mill dust could significantly decrease the ability of resident alveolar macrophages to phagocytize and thereby clear inhaled dust particles. This inhibitory effect would increase the time that particles remain exposed in the lower airway and alveolar spaces and thereby increase the time that potentially toxic compounds in the dust have to exert their biologic effect. This inhibition of macrophage function may therefore contribute to the pathogenesis of byssinosis.