Clearance of immune complexes: role of complement and polymorphonuclear neutrophils

O sistema complemento desempenha um papel importante no transporte e eliminação de imunocomplexos (IC) circulantes. No entanto, existem circunstâncias em que os mecanismos envolvidos não são eficientes, favorecendo a deposição dos IC em órgãos específicos. Tais complexos depositados estimulam a fagocitose pelos polimorfonucleares neutrófilos, com conseqüente produção de radicais de oxigênio e liberação de enzimas lisossomais, e contribuem para a lesão tecidual local. Nesta revisão, damos ênfase ao papel do complemento, bem como dos neutrófilos, na patogênese das doenças por imunocomplexos.The complement system plays an important role in the transport and elimination of circulating immune complexes (IC). However, there are circunstances where the envolved mechanisms fail, leading to deposition of IC at specific organs. The deposited complexes stimulate phagocytosis by polymorphonuclear neutrophils, with production of oxygen radicals and release of lysossomal enzymes, thus contributing to tissular injury. In this review, we discuss the role of complement and neutrophils in pathogenesis of immune complexes diseases

Sensibilização de hemácias de carneiro e restrição à lise pelo sistema complemento do soro eqüino e de carneiro

The effect of the degree of sheep red cell sensitisation by antibody in the resistance to lysis by sheep and horse complement was analysed. The results showed that, as the level of sensitisation increased, so did the homologous complement activity, eventually leading to one hundred percent of lysis; the same was observed for horse serum, generally considered as not efficient at lysing these cells. Therefore, the homologous and heterologous restriction can be overridden by this treatment. This may be of interest for the comprehension of the mechanisms involved in the modulation of the restriction phenomenon in health an in diseases involving complement in domestic animals and in human, as well as in laboratory diagnosis where hemolytic assays are used for measurement of complement activity and evaluation of presence of antibodies in serum samples.Neste trabalho foi analisado o efeito do grau de sensibilização de hemácias de carneiro por anticorpo, na resistência à lise pelo complemento do soro eqüino e de carneiro. Os resultados mostraram que, à medida que houve um aumento do nível de sensibilização, ocorreu também um aumento da atividade do complemento homólogo, levando a 100% de lise; o mesmo foi observado para o complemento do soro eqüino, geralmente considerado ineficiente na lise destas células. A restrição à lise pode, assim, ser sobrepujada por este tratamento. Estes dados podem ser de interesse para a compreensão dos mecanismos envolvidos na modulação do fenômeno de restrição, na saúde e em doenças envolvendo o sistema complemento em animais domésticos e no homem, bem como em diagnóstico laboratorial, onde são utilizados ensaios hemolíticos para medida de atividade do complemento e pesquisa de anticorpos em amostras de soro

Evaluation of the Potential of Brazilian Propolis against UV-Induced Oxidative Stress

This study investigated the potential use of topically and orally administered propolis extracts to prevent UV irradiation-induced oxidative stress in skin. The results illustrated that green propolis extract (GPE) contained greater amounts of polyphenols, coumaric acid, drupanin, baccharin and artepillin C than did brown propolis extract (BPE). GPE showed higher antioxidant activity than BPE when the IC50 (concentration that caused 50% inhibition) values were compared. Interesting, the oral treatment of hairless mice demonstrated a recovery of 30.0% for GPE and 22.8% for BPE with respect to UV irradiation-induced GSH depletion. The topical pretreatment of animals with both propolis extract solutions recovered around 14.0% of the depleted GSH. However, the employed treatments did not inhibit the increase of cutaneous proteinase secretion/activity caused by irradiation. These findings indicate that despite differences in composition and antioxidant properties, GPE and BPE both successfully prevent UV-induced GSH depletion in vivo and are both promising antioxidant systems against oxidative stress in skin. Based on these findings, complementary studies should be performed to enhance our understanding of the protective effects of propolis extracts in skin

Fc γ

Rheumatoid arthritis (RA) is a highly disabling disease that affects all structures of the joint and significantly impacts on morbidity and mortality in RA patients. RA is characterized by persistent inflammation of the synovial membrane lining the joint associated with infiltration of immune cells. Eighty to 90% of the leukocytes infiltrating the synovia are neutrophils. The specific role that neutrophils play in the onset of RA is not clear, but recent studies have evidenced that they have an important participation in joint damage and disease progression through the release of proteolytic enzymes, reactive oxygen species (ROS), cytokines, and neutrophil extracellular traps, in particular during frustrated phagocytosis of immune complexes (ICs). In addition, the local and systemic activation of the complement system contributes to the pathogenesis of RA and other IC-mediated diseases. This review discusses (i) the participation of Fcγ and complement receptors in mediating the effector functions of neutrophils in RA; (ii) the contribution of the complement system and ROS-dependent and ROS-independent mechanisms to joint damage in RA; and (iii) the use of plant extracts, dietary compounds, and isolated natural compounds in the treatment of RA, focusing on modulation of the effector functions of neutrophils and the complement system activity and/or activation

Sensibilização de hemácias de carneiro e restrição à lise pelo sistema complemento do soro eqüino e de carneiro

Neste trabalho foi analisado o efeito do grau de sensibilização de hemácias de carneiro por anticorpo, na resistência à lise pelo complemento do soro eqüino e de carneiro. Os resultados mostraram que, à medida que houve um aumento do nível de sensibilização, ocorreu também um aumento da atividade do complemento homólogo, levando a 100% de lise; o mesmo foi observado para o complemento do soro eqüino, geralmente considerado ineficiente na lise destas células. A restrição à lise pode, assim, ser sobrepujada por este tratamento. Estes dados podem ser de interesse para a compreensão dos mecanismos envolvidos na modulação do fenômeno de restrição, na saúde e em doenças envolvendo o sistema complemento em animais domésticos e no homem, bem como em diagnóstico laboratorial, onde são utilizados ensaios hemolíticos para medida de atividade do complemento e pesquisa de anticorpos em amostras de soro

Sensibilização de hemácias de carneiro e restrição à lise pelo sistema complemento do soro eqüino e de carneiro

Neste trabalho foi analisado o efeito do grau de sensibilização de hemácias de carneiro por anticorpo, na resistência à lise pelo complemento do soro eqüino e de carneiro. Os resultados mostraram que, à medida que houve um aumento do nível de sensibilização, ocorreu também um aumento da atividade do complemento homólogo, levando a 100% de lise; o mesmo foi observado para o complemento do soro eqüino, geralmente considerado ineficiente na lise destas células. A restrição à lise pode, assim, ser sobrepujada por este tratamento. Estes dados podem ser de interesse para a compreensão dos mecanismos envolvidos na modulação do fenômeno de restrição, na saúde e em doenças envolvendo o sistema complemento em animais domésticos e no homem, bem como em diagnóstico laboratorial, onde são utilizados ensaios hemolíticos para medida de atividade do complemento e pesquisa de anticorpos em amostras de soro

Inhibitory activity of liposomal flavonoids during oxidative metabolism of human neutrophils upon stimulation with immune complexes and phorbol ester

Context and objective: The massive production of reactive oxygen species by neutrophils during inflammation may cause damage to tissues. Flavonoids act as antioxidants and have anti-inflammatory effects. In this study, liposomes loaded with these compounds were evaluated as potential antioxidant carriers, in attempt to overcome their poor solubility and stability. Materials and methods: Liposomes containing quercetin, myricetin, kaempferol or galangin were prepared by the ethanol injection method and analyzed as inhibitors of immune complex (IC) and phorbol ester-stimulated neutrophil oxidative metabolism by luminol (CLlum) and lucigenin-enhanced (CLluc) chemiluminescence (CL) assays. The mechanisms involved this activity of liposomal flavonoids, such as cytotoxicity and superoxide anion scavenging capacity, and their effect on phagocytosis of ICs were also investigated. Results and discussion: The results showed that the inhibitory effect of liposomal flavonoids on CLlum and CLluc is inversely related to the number of hydroxyl groups in the flavonoid B ring. Moreover, phagocytosis of liposomes by neutrophils does not seem to necessarily promote such activity, as the liposomal flavonoids are also able to reduce CL when the cells are pretreated with cytochalasin B. Under assessed conditions, the antioxidant liposomes are not toxic to the human neutrophils and do not interfere with IC-induced phagocytosis. Conclusion: The studied liposomes can be suitable carriers of flavonoids and be an alternative for the treatment of diseases in which a massive oxidative metabolism of neutrophils is involved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil) [2006/04398-5, 2007/00161-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [306130/2009-2

Study of quercetin-loaded liposomes as potential drug carriers: in vitro evaluation of human complement activation

Liposomes have been employed as potential drug carriers. However, after their in vivo administration, they can be destabilized by proteins of complement system, contributing to the clearance of vesicles from blood circulation. Antioxidant flavonoids such as quercetin have been reported to be beneficial to human health, but their low water solubility and bioavailability limit their enteric administration. Therefore, the development of appropriate flavonoid-carriers could be of great importance to drug therapy. The aim of the present study was to evaluate the activation of human complement system proteins by liposomes composed of soya phosphatidylcholine (SPC) and cholesterol (CHOL) or cholesteryl ethyl ether (CHOL-OET) loaded with quercetin or not. The consumption of complement, via classical (CP) and alternative (AP) pathways, by different vesicles was evaluated using a hemolytic assay and quantitative determination of iC3b and natural antibodies deposited on empty liposomal surfaces by ELISA. The main results showed that empty liposomes composed of large amounts of CHOL consumed more complement components than the others for both CP and AP. Furthermore, replacement of CHOL with CHOL-OET reduced complement consumption via both CP and AP. Incorporation of quercetin did not change CP and AP consumption. Deposition of iC3b, IgG and IgM in vesicles composed of SPC: CHOL-OET at a molar ratio of 1.5:1 was lower compared to the others. Taken together, these observations suggest that liposomes composed of SPC: CHOL-OET at a molar ratio of 1.5:1 are the most appropriate among the vesicles studied herein to be used as a drug carrier system in further investigations.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil) [2006/04398-5, 2007/00161-3