pH敏感含糖三元共聚水凝胶Poly(AM-CO-IA-VBG)的药物释放性能研究

用4-乙烯基苄基胺与葡萄糖内酯反应合成了4-乙烯苄基葡萄糖酰胺单体(VBG)。以亚甲基双丙烯酰胺(BisA)为交联剂,用过硫酸钾(KPS)引发丙烯酰胺(AM)、衣康酸(IA)及4-乙烯苄基葡萄糖酰胺使之共聚,得到pH敏感含糖结构的三元共聚水凝胶。用核磁共振及红外光谱对单体和水凝胶的结构进行了表征,研究了不同水凝胶中药物的释放性能,以及pH值及盐的浓度对水凝胶中药物释放的影响。结果表明:水凝胶中药物在低pH值时或盐中药物释放显著下降,表明水凝胶对酸或盐有强烈的响应性。     

纳米羟基磷灰石/阿司匹林/聚乙烯醇/明胶/海藻酸钠水凝胶支架的制备与表征

背景：阿司匹林是经典非类固醇抗炎药物,合适剂量的阿司匹林可调节免疫、促进成骨。制备出可缓释阿司匹林、调控骨缺损区免疫微环境和加速骨缺损修复的骨组织工程材料是目前的研究热点。目的：制备可调控免疫微环境和加速骨缺损修复的新型水凝胶支架。方法：制备含有质量分数0%,10%和20%纳米羟基磷灰石的纳米羟基磷灰石/阿司匹林/聚乙烯醇/明胶/海藻酸钠水凝胶支架,对水凝胶支架的微观结构、孔隙率、化学成分、晶相结构、药物缓释性能、力学性能、溶胀性能和降解性能进行表征。通过细胞增殖和细胞毒性实验评价水凝胶支架的生物相容性。结果与结论：(1)扫描电镜和孔隙率检测结果表明,0%,10%纳米羟基磷灰石组水凝胶支架具有更仿生的层级多孔结构、孔隙通联性和孔隙率;(2)傅里叶红外光谱和X射线衍射结果表明,水凝胶支架内各原料以物理、化学双交联方式结合,且不会破坏纳米羟基磷灰石的晶相结构;(3)力学性能结果表明,10%纳米羟基磷灰石组水凝胶支架具有最佳的压缩模量和压缩强度;(4)药物释放性能结果显示,随着纳米羟基磷灰石质量的增加,水凝胶支架的阿司匹林累计释放率降低,但是药物突释率降低、缓释时间延长;(5)溶胀性能和降解...     

琥珀酸美托洛尔HPMC骨架片释放影响因素研究

以羟丙基甲基纤维素（HPMC）为骨架材料，乙基纤维素（EC）为阻滞剂，采用湿颗粒压片法制备琥珀酸美托洛尔亲水凝胶骨架片，考察HPMC用量、HPMC黏度、EC用量、制备方法、压片压力、释放介质及转速对琥珀酸美托洛尔（MS）骨架片体外释药的影响。结果表明，MS骨架片体外释药符合Higuchi方程，药物释放机制是骨架溶蚀和药物扩散的综合效应；HPMC用量与黏度、阻滞剂用量、制备方法、压片压力对释放速率均有显著性影响；释放介质的pH值及转速对释放速率无显著性影响。     

聚乙烯醇/丙烯酰胺接枝共聚物水凝胶的制备及表征

背景：交联水凝胶主要是使大分子链形成网状结构,网固交联基质,这样所得的水凝胶力学性能和透明性相对较差。 目的：采用自由基聚合机制制备聚乙烯醇/丙烯酰胺接枝共聚物水凝胶。 方法：以聚乙烯醇分子作为主链,聚乙烯醇分子中羟基为接枝点,共价接入丙烯酰胺单体。考察反应温度、时间、单体用量和引发剂用量对产物接枝率的影响,通过红外光谱表征聚乙烯醇/丙烯酰胺接枝共聚物共聚物的化学结构。 结果与结论：接枝聚合反应最佳反应条件：引发剂浓度0.04 mol/L、丙烯酰胺/聚乙烯醇(侧羟基)摩尔比6∶1、在40 ℃条件下反应4 h。经过FTIR分析,确认丙烯酰胺与聚乙烯醇发生了聚合反应;经过平衡溶胀测试,分析了接枝聚合物与聚乙烯醇的溶胀率随温度的变化关系,进一步证实了接枝聚合反应的发生,验证了接枝聚乙烯醇/丙烯酰胺接枝共聚物具有明显的温敏性能。      

可注射明胶透明质酸钠水凝胶药物载体的制备

目的制备可注射明胶透明质酸钠水凝胶药物载体,为临床应用提供依据。方法利用现有临床材料医用透明质酸钠水凝胶和医用可吸收明胶海绵加以物理混合制备成可注射水凝胶,用荧光染料罗丹明B作为模拟药物并应用Franz扩散池评价该水凝胶的体外药物释放率,通过CCK-8法检测成纤维细胞(L929)的活性,通过小动物活体成像评价药物在豚鼠听泡内的分布与扩散。结果明胶透明质酸水凝胶呈凝胶状,具有可注射性、对L929细胞具有良好的相容性,对罗丹明B的体外缓释效果良好,72h的累积释放率可达42.3%。注入豚鼠听泡后可滞留72h以上,并贴附于圆窗膜上。结论成功制备了可注射明胶透明质酸钠水凝胶药物缓释载体,具有潜在的临床应用价值。     

左旋多巴改性有机-无机复合药物洗脱支架涂层的制备

背景:目前,药物主要是通过支架表面的涂层实现其装载和释放,且使用的药物装载涂层材料多为高分子材料。但临床研究发现,高分子材料使用带来的后期血栓问题以及植入后基体表面涂层完整性不被破坏成为新的挑战。目的:制备一种新型的有机-无机复合涂层作为支架药物载体,在降低高分子的使用并实现药物缓释同时保持涂层弹性及涂层与基体间良好的粘结性。方法:采用溶胶凝胶法在316L不锈钢表面制备左旋多巴改性的二氧化硅-聚乙二醇涂层。以阿司匹林为示范药物,研究药物装载方式对释放动力学的影响。通过金相显微镜观察涂层表面形貌,用紫外可见光谱测其释放动力学。结果与结论:左旋多巴改性二氧化硅-聚乙二醇涂层与基体结合良好,克服了原涂层容易开裂、剥落的现象。溶胶凝胶过程中引入阿司匹林能够实现药物在40h内缓慢线性释放,而通过浸泡扩散实现药物装载的涂层,1h内释放出总装载量的75%,出现了药物爆释现象。实验成功制备了一种新型的药物可控释性有机-无机复合涂层材料,左旋多巴A的黏结性和自交联性可以很好地解决涂层与基体黏结性差、涂层容易开裂弹性差等问题。在溶胶凝胶过程中同时装载的阿司匹林能够实现在基质中的线性释放,避免了爆释现象。     

制备表面图案化的聚丙烯酰胺-丙烯酸水凝胶

背景:聚丙烯酰胺水凝胶具备良好的生物相容性,但力学性能较差,影响了其在生物材料领域的应用。目的:通过微模塑图形化压印制备具有特殊尺寸的聚丙烯酰胺-丙烯酸水凝胶。方法:依次将不同体积的聚丙烯酰胺溶液、丙烯酸与过硫酸铵溶液混合,加入含有微模塑图形化印章的孔板中,制备聚丙烯酰胺-丙烯酸水凝胶:A组聚丙烯酰胺溶液1.4 mL,丙烯酸0.1 mL;B组聚丙烯酰胺溶液1.3 mL,丙烯酸0.2 mL;C组聚丙烯酰胺溶液1.2 mL,丙烯酸0.3 mL;D组聚丙烯酰胺溶液1.1 mL,丙烯酸0.4 mL;E组聚丙烯酰胺溶液1.0 mL,丙烯酸0.5 mL;F组聚丙烯酰胺溶液0.9 mL,丙烯酸0.6 mL。6组过硫酸铵溶液均为50 L。光镜下观察水凝胶的图案化结构,电子万能试验机检测水凝胶的力学性能。结果与结论:光镜显示各组水凝胶表面的条纹清晰可见;丙烯酸的加入有效改良了水凝胶的力学性能,随着丙烯酸比例的不断增加,水凝胶的力学性能逐渐增强。结果表明,聚丙烯酸-丙烯酰胺水凝胶具有良好的力学性能,有望在组织工程损伤修复领域具有良好的应用前景。     

载银水凝胶或载抗生素壳聚糖水凝胶在抑菌性能和细胞毒性方面的研究

目的研究壳聚糖水凝胶,壳聚糖载银水凝胶和壳聚糖载抗生素水凝胶短期的抑菌功效和细胞毒性。方法通过添加交联剂后制备壳聚糖水凝胶,并有效装载银离子或硫酸庆大霉素。进行抑菌实验和累计释放实验了解壳聚糖基水凝胶的抗菌性能和药物控释性。通过使用材料的浸提液检测这三种水凝胶的细胞毒性。结果抑菌实验结果表明壳聚糖水凝胶,壳聚糖载银水凝胶和壳聚糖载抗生素水凝胶均能有效抑制金黄色葡萄球菌的增殖。且壳聚糖载抗生素水凝胶具有最佳的抑菌性能且极大地抑制了生物膜的形成。体外药物释放显示抗生素在7天内的累计释放多于60%;而银离子的释放低于10%。细胞毒性实验表明这三个凝胶材料无明显细胞毒性。结论壳聚糖基水凝胶具有良好的短期抑菌效果,可降解,且无明显细胞毒性,在骨科应用方面有着巨大的前景。     

温敏型可注射水凝胶的制备研究

为得到应用于软组织重建的新型可注射组织工程支架材料,将经交联合成的HA交联凝胶(XLHA),分别与降解性能不同的两种温敏型材料聚N-异丙基丙烯酰胺(PNIPAAm)凝胶和甲基纤维素(MC),在常温下共混合成XLHA-PNIPAAm与XLHA-MC可注射水凝胶,分析XLHA-PNIPAAm与XLHA-MC水凝胶的可注射性能、耐酶解性能、温敏性能和化学结构,并进行溶血试验与细胞毒性试验评价可注射凝胶的生物相容性。研究获得了XLHA-PNIPAAm的可注射水凝胶的制备条件,并证实了分别将不可降解材料PNIPAAm与可降解材料MC和HA共混均能有效延缓HA的降解,且PNIPAAm延缓HA降解的效果更为显著。辐照剂量为5 kGy,MBAAm/NIPAAm(M/M)=0.015,NIPAAm单体浓度为3%,制备的PNIPAAm与XLHA共混制备的XLHA-PNIPAAm可注射凝胶的耐酶解性能最佳。差示扫描量热仪(DSC)检测显示XLHA-PNIPAAm的温敏性较为稳定。两种复合凝胶的细胞毒性和溶血试验均合格,且XLHA-PNIPAAm水凝胶的生物相容性要好于XLHA-MC凝胶。     

温敏型凝胶的缓释作用与临床应用

文题释义：温敏型凝胶：是一种特殊的水凝胶,能根据一定温度从流动的液体(溶胶相)转变为非流动的水凝胶(凝胶相)。因其特性,在生物医学和制药方面有广泛的应用,即药物输送、细胞培养、组织工程等。聚N-异丙基丙烯酰胺：由单体N-异丙基丙烯酰胺聚合而成,其大分子链上同时具有亲水性的酰氨基和疏水性的异丙基,使线型聚N-异丙基丙烯酰胺的水溶液及交联后的聚N-异丙基丙烯酰胺水凝胶呈现温度敏感特性。 背景：温敏型凝胶是近年来兴起的一种药物新剂型,因其具有缓释、控释、靶向给药等优势而成为近年来的研究热点。 目的：总结搜索文献中温敏型凝胶各种缓释机制,以及温敏型凝胶在临床上的应用疗效。 方法：在万方、中国知网、维普、PubMed、谷歌学术等数据库中,以“温敏型凝胶,缓释,给药途径”为中文检索词,以“thermosensitive gel,sustained release,administration route”为英文检索词检索温敏型凝胶缓释机制及临床应用方面的文章。结果与结论：①温敏型凝胶具有最低临界溶解温度,能随环境温度改变而发生一定程度的相变,比其他剂型有更多的优势,能使药物在人体内发挥很好的缓释作用,降低药物毒性,防止药物外渗,并提高药物的稳定性,还具有很好的临床应用前景;②温敏型凝胶有着注射、口腔、耳内、鼻腔、眼内、皮肤等多种给药方式,具有广泛的应用前景。但是各种凝胶材料都存在不同缺点,比如天然生物材料具有可塑性差、机械强度不足、容易被病原微生物污染、难以大量生产的缺点,人工合成材料往往亲水性还不够,而且温敏型凝胶在体内的代谢途径对组织器官的影响也尚在研究中。 ORCID: 0000-0002-9070-7602(陈泳佳) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Detection and characterization of autoagglutination activity by Campylobacter jejuni

In several gram-negative bacterial pathogens, autoagglutination (AAG) activity is a marker for interaction with host cells and virulence. Campylobacter jejuni strains also show AAG, but this property varies considerably among strains. To examine the characteristics of C. jejuni AAG, we developed a quantitative in vitro assay. For strain 81-176, which shows high AAG, activity was optimal for cells grown for < or = 24 h, was independent of growth temperature, and was best measured for cells suspended in phosphate-buffered saline at 25 degrees C for 24 h. AAG activity was heat labile and was abolished by pronase or acid-glycine (pH 2.2) treatment but not by lipase, DNase, or sodium metaperiodate. Strain 4182 has low AAG activity, but extraction with water increased AAG, suggesting the loss of an inhibitor. Strain 6960 has weak AAG with no effect due to water extraction. Our study with clinical isolates suggests that C. jejuni strains may be grouped into three AAG phenotypes. A variant derived from strain 81116 that is flagellate but immotile showed the strong AAG exhibited by the parent strain, suggesting that motility per se is not necessary for the AAG activity. AAG correlated with both bacterial hydrophobicity and adherence to INT407 cells. Mutants which lack flagella (flaA, flaB, and flbA) or common cell surface antigen (peb1A) were constructed in strain 81-176 by natural transformation-mediated allelic exchange. Both AAG activity and bacterial hydrophobicity were abolished in the aflagellate mutants but not the peb1A mutant. In total, these findings indicate that C. jejuni AAG is highly associated with flagellar expression.     

Mononuclear cells in acute allograft glomerulopathy.

A distinctive glomerular lesion of renal allografts, acute allograft glomerulopathy (AAG), is characterized by hypercellularity and endothelial cell hypertrophy and injury. For elucidating the pathogenesis of this lesion, the infiltrating cells were analyzed by light- and electron-microscopic immunoperoxidase techniques with monoclonal antibodies and compared with those in cellular rejection without AAG (non-AAG). Substantial numbers of T lymphocytes (CD3+,Leu-4+) were detected in the glomeruli in AAG (11.4 +/- 2.4 cells per glomerular cross-section), whereas very few were found in non-AAG (1.4 +/- 1.8, P less than 0.001). In AAG the CD8+ (Leu-2a) subset accounted for essentially all of the intraglomerular T cells, which had a lower CD4/CD8 ratio than the corresponding peripheral blood lymphocytes (P less than 0.03). AAG also differed from non-AAG by the accumulation of intraglomerular mononuclear cells that expressed HNK-1 antigen (Leu-7) and mononuclear phagocytes, which were identified by the presence of the monocyte fibronectin receptor (A6F10). Intraglomerular mononuclear cells were positive for the interleukin-2 receptor (IL2R) and HLA Class II antigens (HLA-DR). The glomeruli in AAG stained more intensely for HLA Class I antigens than the tubules, in contrast to non-AAG cases (P less than 0.03). The interstitial infiltrates in AAG grafts were less intense than in non-AAG of similar duration (P less than 0.01) and had a lower CD4/CD8 ratio, whereas arterial intimal infiltrates were more severe in AAG (P less than 0.03) and consisted of CD8+, but not CD4+, cells. Pathologic features that correlated with poor graft survival were increased numbers of intraglomerular CD8+ cells (both AAG and non-AAG), fewer interstitial T cells (AAG), and more interstitial CD8+ cells (non-AAG) (all P less than 0.05). Cytomegalovirus (CMV) infection was detected in all (8/8) patients with AAG who were studied for infection before or within 3 weeks after the biopsy, compared with 3 of 9 patients with non-AAG. It is proposed that acute allograft glomerulopathy is a distinct form of T-cell-mediated allograft rejection, sometimes associated with CMV infection, in which the glomerular endothelium, often with the arterial endothelium, becomes the principal target of CD8+ T cells.     

阿司匹林对炎症条件下人血管内皮细胞一氧化氮的产生及诱导型一氧化氮合酶mRNA表达的影响

目的:探讨炎症时阿司匹林(AS)对内皮细胞一氧化氮(NO)的产生及诱导型一氧化氮合酶(iNOS)基因表达的抑制作用。方法:Griess法测上清液NO^-₂/NO^-₃水平、黄递酶法测NOS活性、常规生化法测乳酸脱氢酶(LDH)、丙二醛(MDA)浓度,染料排除法测细胞活力,RT-PCR技术分析iNOSmRNA水平。结果:白介素(IL)-1β、肿瘤坏死因子(TNF)-α、γ-干扰素(INF)联用脂多糖(LPS)诱导后上清液中NO^-₂/NO^-₃由(4.27±0.75)μmol/L增加到(9.35±1.25)μmol/L,对内皮细胞造成明显的损伤。但3mmol/LAS组NO生成及NOS活性明显降低,LDH释放率及MDA浓度下降,细胞存活率上升,与NO诱导组相比差异显著。并随AS剂量的增加对NO的抑制及对细胞的保护作用更加明显,但AS对生理水平的NO没有抑制作用。同时发现10mmol/L浓度以下AS对iNOSmRNA表达水平没有影响;但10-20mmol/L的AS则可在转录水平上抑制iNOSmRNA的表达。并观察到水杨酸钠及消炎痛不具有抑制NO产生的作用。结论:AS具有明显抑制IL-1β、TNF-α、γ-INF及LPS诱导NO生成的作用,从而保护血管内皮细胞避免炎症时高浓度NO的损伤。     

Serum free and bound sialic acid and alpha-1-acid glycoprotein in patients with laryngeal cancer

Serum specimens from 35 patients with laryngeal cancer (10 at stage II; 12 at stage III; 1.3 at stage IV) were obtained before therapy was initiated. Concentrations of bound sialic acid (BSA), free sialic acid (FSA), and alpha-1-acid glycoprotein (AAG) were compared to those in serum specimens from 34 healthy controls. The mean levels of serum BSA and AAG were significantly increased in the laryngeal cancer patients versus the controls; there was no significant difference in serum FSA levels between the patients and controls. Mean serum BSA and AAG levels were lowest in the control group and highest in the stage IV patients. As the stage of the cancer advanced, progressively higher levels of serum BSA and AAG were observed. The results indicate that serum BSA and AAG, but not FSA, show correlation with the stage of laryngeal carcinoma.     

Interactions of alpha1-acid glycoprotein with the immune system. I. Purification and effects upon lymphocyte responsiveness.

Alpha1-acid glycoprotein (AAG) is a constituent of normal serum which is elevated in concentration in the acute phase of inflammation; its physical and chemical properties have been defined but its biological function is uncertain. In the present study, the effect of AAG on the proliferative response of lymphocytes to several different stimuli was determined. For this purpose AAG was prepared by precipitation of human ascites fluid with sulphosalicylic acid and passage of the supernate through SP-Sephadex; the eluted protein migrated as a single band during immunoelectrophoresis, polyacrylamide gel electrophoresis and chromatography on Bio-Gel-A-1-5 m in 6 M guanidine HCl. This AAG was found to markedly inhibit the proliferative response of human peripheral blood lymphocytes to PHA; it also inhibited blastogenesis induced by Con A and PWM, but to a lesser extent. AAG was not cytotoxic to lymphocytes, and its inhibitory effects were reversed at higher mitogen concentrations. Lymphocytes preincubated with AAG remained less reactive to PHA indicating that, although AAG appeared to react with PHA, its effect was directed predominantly to the cell. Further, AAG markedly inhibited the mixed lymphocyte response, and this effect was directed to the responder cells. Thus, AAG is another acute phase reactant with the ability to modulate lymphocyte responsiveness.     

Human α-1-acid Glycoprotein Inhibits TNF Production in the CNS of Rabbits with Meningitis: A Report of Preliminary Observations

Bacterial meningitis is accompanied by an acute inflammatory response which may be exacerbated by antibiotic treatment and subsequent killing of bacteria. Bacterial cell products induce the release of cytokines including TNF, which contribute to the inflammatory process. Alpha-1-acid glycoprotein (AAG), an acute phase reactant, is elevated during inflammation. To test whether AAG has anti-inflammatory activity we examined its effect on lipopolysaccharide-stimulated human peripheral blood mononuclear cells. Treatment of the cells with AAG in vitro resulted in reduced TNF production. To test the effects of the molecule in vivo, AAG was administered intrathecally to rabbits with Haemophilus influenzae B lysate induced meningitis. Human AAG reduced TNF production and leukocytosis in the cerebrospinal fluid. Histopathology of the leptomeninges showed markedly attenuated inflammation. These results indicate that AAG can reduce inflammation in rabbits with experimental meningitis and that the effect may be directly on TNF production by stimulated mononuclear leukocytes.     

C-reactive protein and alpha 1-acid glycoprotein levels in dogs infected with Ehrlichia canis.

To elucidate whether acute-phase protein responses occur in dogs infected with Ehrlichia canis, C-reactive protein (CRP) and alpha 1-acid glycoprotein (AAG) levels were serially measured in the plasma of five dogs experimentally inoculated with E. canis and 10 sham-inoculated or noninoculated control dogs. The CRP concentration was measured by a canine-specific capture enzyme-linked immunosorbent assay, and the AAG concentration was measured by a canine-specific radial immunodiffusion method. In all E. canis-inoculated dogs, a 3.3- to 6.5-fold increase in the plasma CRP concentration and a 1.9- to 8.6-fold increase in the plasma AAG concentration over the preinoculation level occurred at days 4 to 6 postexposure. Despite the persistence of E. canis and high antibody titers, both CRP and AAG concentrations gradually declined to preexposure levels by day 34 postexposure. E. canis-infected dogs had mild and transient clinical signs which resolved without treatment by day 14 postexposure. The CRP and AAG concentrations in control inoculated or nontreated dogs remained within the normal range throughout the experimental period. Of 12 dogs naturally infected with E. canis, 75% had greater than 50 micrograms of CRP per ml and 83% had greater than 500 micrograms of AAG per ml. All of these 12 dogs had chronic and severe clinical signs of canine ehrlichiosis. Thus, elevations in the levels of acute-phase proteins occur in both acute and chronic canine ehrlichiosis. Determination of CRP and AAG concentrations may help in assessing the severity of inflammatory damage in dogs with E. canis infections.     

Serum alpha-1 acid glycoprotein in chronic renal failure and hemodialysis

The total concentration and concanavalin A (ConA)-dependent microheterogeneity of alpha-1 acid glycoprotein (AAG) were studied in thirty hemodialyzed uremic patients and eighteen non-dialyzed uremic patients, by comparison with healthy volunteers. Serum concentrations of AAG were significantly higher in the non-dialyzed uremic (1.27 +/- 0.47 g/l) and hemodialyzed patients (1.29 +/- 0.33 g/l) than in the volunteers (0.79 +/- 0.09 g/l). The proportions of strongly ConA-reactive AAG fractions were also higher in non-dialyzed uremic (16.7%) and hemodialyzed patients (18.5%) than in volunteers (14.1%). These data may be related to an increase in bi-antennary glycans, as observed in patients on peritoneal dialysis, together with a probable change in sialylation. AAG serum levels and microheterogeneity were similar in non-dialyzed and hemodialyzed patients and did not appear in the dialyzed patients to depend on the type of dialysis membrane used, i.e. cuprophan (CU), cellulose acetate (CA), hemophan (HE), polyacrylonitrile (PAN), and polysulfon (PS), in spite of differences in biocompatibility. In patients dialyzed with CA membranes, there was a distinct decrease in the ConA non-reactive fraction (38.0%) and an increase in ConA slightly-reactive (42.2%) and strongly-reactive (19.7%) fractions. Differences in AAG serum levels and ConA reactivity between patients dialyzed with CA and PAN membranes seem to justify further investigations of other acute-phase reactants and immunological parameters.     

Alpha-1-Acid (AAG, Orosomucoid) Glycoprotein: Interaction with Bacterial Lipopolysaccharide and Protection from Sepsis

In the acute phase response to a variety of insults a rise in the levels of the acute phase proteins, including elevations of serum ₁ acid glycoprotein (AAG) occurs. The physiological role of AAG is unknown, however, the time course of AAG production in the acute phase response together with its strong affinity for basic compounds suggests that AAG may function as an immune modulator to bind both exogenous and endogenous inflammatory mediators. Using E. coli lipopolysaccharide (LPS), an initiator of the acute inflammatory response associated with septic shock, we demonstrate that AAG-LPS complexes can activate mouse macrophages in vitro. In a mouse animal model of sepsis, AAG was shown to protect against meningococcal endotoxin.To pursue the mechanism of AAG action we demonstrated that AAG interacts directly with LPS using dynamic light scattering particle sizing and particle mobility. We also determined the enthalpy of interaction of AAG and LPS and showed that AAG leads to agglutination of LPS impregnated rabbit red blood cells.These studies suggest that AAG may function as an immune-modulator in the acute phase response, possibly by counter-regulating the activity of macrophage pro-inflammatory cytokines.