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31.
《MABS-AUSTIN》2013,5(2):409-421
Antibody-dependent cell-mediated cytotoxicity (ADCC) has been suggested as an essential mechanism for the in vivo activity of cetuximab, an epidermal growth factor receptor (EGFR)-targeting therapeutic antibody. Thus, enhancing the affinity of human IgG1 antibodies to natural killer (NK) cell-expressed FcγRIIIa by glyco- or protein-engineering of their Fc portion has been demonstrated to improve NK cell-mediated ADCC and to represent a promising strategy to improve antibody therapy. However, human polymorphonuclear (PMN) effector cells express the highly homologous FcγRIIIb isoform, which is described to be ineffective in triggering ADCC. Here, non-fucosylated or protein-engineered anti-EGFR antibodies with optimized FcγRIIIa affinities demonstrated the expected benefit in NK cell-mediated ADCC, but did not mediate ADCC by PMN, which could be restored by FcγRIIIb blockade. Furthermore, eosinophils and PMN from paroxysmal nocturnal hemoglobinuria patients that expressed no or low levels of FcγRIIIb mediated effective ADCC with FcγRIII-optimized anti-EGFR antibody. Additional experiments with double FcγRIIa/FcγRIII-optimized constructs demonstrated enhanced PMN-mediated ADCC compared with single FcγRIII-optimized antibody. In conclusion, our data demonstrate that FcγRIIIb engagement impairs PMN-mediated ADCC activity of FcγRIII-optimized anti-EGFR antibodies, while further optimization of FcγRIIa binding significantly restores PMN recruitment. 相似文献
32.
Environmental stress and endocrine control can affect pathogenesis of sexually transmitted diseases such as trichomoniasis. Acute Tritrichomonas foetus infection was compared in female BALB/c mice to infections in mice treated with high doses of estradiol or housed in constant bright illumination (stressed). In untreated mice, T. foetus readily colonized the reproductive tract, causing minimal epithelial damage and inflammation. Several fold increases of IFN-gamma, TNF-alpha, MCP-1, and IL-6 cytokines were detected after estradiol-treatment of mice, resulting in greatly enhanced inflammation and tissue damage throughout the reproductive tract. Interestingly, estradiol-treatment of mice resulted in reduced T. foetus colonization compared to untreated mice. Infection in stressed mice resulted in increased tissue damage, inflammation, and inflammatory cytokine expression, although parasite colonization within the reproductive tract was similar to that in untreated mice. These results indicate that either estradiol-treatment or stress result in pathogenesis often observed during severe disease. Alternatively, infection in non-treated mice results in chronic colonization, with little inflammation or pathology. 相似文献
33.
Stefanie Derer Pia Glorius Martin Schlaeth Stefan Lohse Katja Klausz Umesh Muchhal John R Desjarlais Andreas Humpe Thomas Valerius Matthias Peipp 《MABS-AUSTIN》2014,6(2):409-421
Antibody-dependent cell-mediated cytotoxicity (ADCC) has been suggested as an essential mechanism for the in vivo activity of cetuximab, an epidermal growth factor receptor (EGFR)-targeting therapeutic antibody. Thus, enhancing the affinity of human IgG1 antibodies to natural killer (NK) cell-expressed FcγRIIIa by glyco- or protein-engineering of their Fc portion has been demonstrated to improve NK cell-mediated ADCC and to represent a promising strategy to improve antibody therapy. However, human polymorphonuclear (PMN) effector cells express the highly homologous FcγRIIIb isoform, which is described to be ineffective in triggering ADCC. Here, non-fucosylated or protein-engineered anti-EGFR antibodies with optimized FcγRIIIa affinities demonstrated the expected benefit in NK cell-mediated ADCC, but did not mediate ADCC by PMN, which could be restored by FcγRIIIb blockade. Furthermore, eosinophils and PMN from paroxysmal nocturnal hemoglobinuria patients that expressed no or low levels of FcγRIIIb mediated effective ADCC with FcγRIII-optimized anti-EGFR antibody. Additional experiments with double FcγRIIa/FcγRIII-optimized constructs demonstrated enhanced PMN-mediated ADCC compared with single FcγRIII-optimized antibody. In conclusion, our data demonstrate that FcγRIIIb engagement impairs PMN-mediated ADCC activity of FcγRIII-optimized anti-EGFR antibodies, while further optimization of FcγRIIa binding significantly restores PMN recruitment. 相似文献
34.
Recovery of metals from the polymetallic sea nodules at the pilot plant at National Metallurgical Laboratory, Jamshedpur, India has generated a highly toxic effluent. This effluent contains several metals like Mn, Cu, Zn, Fe, Pb, Cr, and Cd that pollute the neighboring water bodies when discharged. Hence detoxification of this effluent was practiced using two plants: Lemna minor and Azolla pinnata for 7 days. During investigation A. pinnata removed 96% of Mn, 97% of Cu, 98% of Zn, 70% of Fe, 96% of Pb, 93% of Cr, 78% of Cd, and was comparatively more effective than L. minor which removed 94% of Mn, 86% of Cu, 62% of Zn, 74% of Fe, 84% of Pb, 63% of Cr, 78% of Cd. During the 7 days of experiment chlorophyll content decreased by 51% and 59% in A. pinnata and L. minor respectively. Based on our findings we can suggest that these two plants have wide range of metal retention potentialities hence can be of routine use for purification of toxic effluents. 相似文献
35.
Calich VL da Costa TA Felonato M Arruda C Bernardino S Loures FV Ribeiro LR de Cássia Valente-Ferreira R Pina A 《Mycopathologia》2008,165(4-5):223-236
Innate immunity is based in pre-existing elements of the immune system that directly interact with all types of microbes leading
to their destruction or growth inhibition. Several elements of this early defense mechanism act in concert to control initial
pathogen growth and have profound effect on the adaptative immune response that further develops. Although most studies in
paracoccidioidomycosis have been dedicated to understand cellular and humoral immune responses, innate immunity remains poorly
defined. Hence, the main purpose of this review is to present and discuss some mechanisms of innate immunity developed by
resistant and susceptible mice to Paracoccidioides brasiliensis infection, trying to understand how this initial host-pathogen interface interferes with the protective or deleterious adaptative
immune response that will dictate disease outcome. An analysis of some mechanisms and mediators of innate immunity such as
the activation of complement proteins, the microbicidal activity of natural killer cells and phagocytes, the production of
inflammatory eicosanoids, cytokines, and chemokines among others, is presented trying to show the important role played by
innate immunity in the host response to P. brasiliensis infection. 相似文献
36.
Antonio Bretan̄a JoséLuis Avila Gustavo Lizardo Jacinto Convit Antonio José Rondón 《Experimental parasitology》1983,55(3):377-385
Experimental nodules of American leishmaniases were obtained by inoculating 0.1–1 × 105 amastigotes into the dorsum of the hindpaws of golden hamsters and of C57B1/6J mice. The amastigotes were obtained by biopsy of lesions in six human cases of cutaneous leishmaniases and were serially maintained in golden hamsters and in a fetal calf serum-containing medium. Human nodules were obtained by biopsy from several patients with diffuse cutaneous leishmaniases, always prior to treatment. Within the same host species, no ultrastructural differences were seen in the tissue response to isolates of Leishmania mexicana, L. brasiliensis, or L. garnhami, nor were there differences between the host species in response to a particular isolate of the genus Leishmania. The typical inflammatory response was a macrophage granuloma with abundant polymorphonuclear neutrophils, some eosinophils, and plasma cells. Simple human cutaneous leishmanial lesions, as well as experimental nodules in regression, show many fibroblasts, much collagen fiber, but very few parasites. In typical lesions, parasites occurred within macrophage phagolysosomes, within distended lacunar cells, and in the intercellular spaces. Leishmaniae strongly adhered to parasitophorous vacuoles by a site of their plasma membrane directly opposite the flagellum, and the host cell cytoplasm close to the adherence site became highly vacuolated. In most cases the intra- and extracellular parasites show normal morphology, which suggest the inability of phagocytic cells to attack them. 相似文献
37.
Leukotriene B4 is a complete secretagogue in human neutrophils: a kinetic analysis 总被引:18,自引:0,他引:18
C N Serhan A Radin J E Smolen H Korchak B Samuelsson G Weissmann 《Biochemical and biophysical research communications》1982,107(3):1006-1012
The interactions have been studied of leukotriene B4 (LTB4) and 20-COOH-LTB4 with human neutrophils (PMN). Kinetic studies, utilizing continuous recording techniques, showed that LTB4 activates PMN with respect to aggregation, mobilization of membrane-associated Ca2+, generation, and degranulation within seconds of exposure. Dose-response studies indicate 1) that LTB4 is much more potent than its dicar?ylic acid derivative (20-COOH-LTB4) or its all trans-isomer, and 2) that PMN responses to these agents are largely dependent upon pretreatment of the cells with cytochalasin B. These properties were similar to those of the microbial ionophores, ionomycin and A23187. Results demonstrate that LTB4 rapidly activates PMN and indicate that LTB4 serves as a complete secretagogue. Moreover, they provide additional evidence that oxidized fatty acids activate human PMN. 相似文献
38.
The superoxide anion and singlet molecular oxygen: their role in the microbicidal activity of the polymorphonuclear leukocyte 总被引:26,自引:0,他引:26
R C Allen S J Yevich R W Orth R H Steele 《Biochemical and biophysical research communications》1974,60(3):909-917
Superoxide dismutase was found to partially inhibit both chemiluminescence and nitroblue tetrazolium (NBT) reduction from intact human polymorphonuclear leukocytes. This capacity to reduce NBT was lost when the polymorphonuclear leukocytes were sonicated, but could be regained if exogenous NADPH (or NADH) was added to the system. Superoxide dismutase was found to inhibit this NADPH- and NADH-dependent NBT reduction. A mechanism is proposed that relates superoxide anion generation to the univalent reduction of O2 by the activated NADPH (and NADH) oxidase. The relationship of superoxide anion production to NBT reduction, singlet molecular oxygen generation, and chemiluminescence is discussed. 相似文献
39.
Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals 总被引:12,自引:0,他引:12
Baolu Zhao Xiaojie Li Rungen He Shujun Cheng Xin Wenjuan 《Cell biochemistry and biophysics》1989,14(2):175-185
With the use of the spin trapping methods, the scavenging effects of the extracts of green tea and other natural foods are
studied. In stimulated polymorphonuclear leukocytes (PMN) system, water extract fraction 6 (F6) from green tea and green tea
polyphenols (GTP) have the strongest scavenging effect on the active oxygen radicals, much stronger than vitamin C (Vc) and,
vitamin E (Ve). Rosemary antioxidants (RA) and Curcumin (Cur) have weaker scavenging effects than Vc, but stronger thanVe. In Fenton Reaction, Cur has the strongest scavenging effect (69%) on hydroxyl radicals. In irradiation, riboflavin system
F6(74%) and GTP(72%) have very strong scavenging effects that are weaker than Vc, but much stronger thanVe (23%). With the use of spin probe oxymetry, the oxygen consumption in respiratory burst of stimulated PMN were measured when
the antioxidants existed in these systems The results demonstrated that these antioxidants did not affect the respiratory
burst of human polymorphonuclear leukocytes stimulated with PMA. 相似文献
40.
M Deleers J P Servais F de Laveleye E Wulfert 《Biochemical and biophysical research communications》1984,123(1):178-185
Egg yolk phosphatidyl choline liposomes containing variable amounts of phosphatidyl ethanolamine, phosphatidyl inositol or phosphatidyl serine demonstrated important variations in the fluorescence of 3.3' dipropylthiodicarbocyanine. When the membrane contained no cholesterol, fluorescence was not correlated with membrane fluidity as measured by diphenyl hexatriene polarization. Increasing cholesterol concentration in valinomycin containing liposome membranes decreased the potassium induced apparent membrane potential and prevented sorption of dye to the membrane. Discontinuity in the apparent potential occurred at 30 mol% cholesterol but could not be correlated with changes in microviscosity. These results indicate that great care should be taken when correlating rapid variations of fluorescence to changes in membrane potential. We propose that changes in phospholipid metabolism could well explain fluorescent changes when monitoring the fluorescence of cyanine dye molecules sorbed to biological membranes. 相似文献