Interleukin-15 increases Paracoccidioides brasiliensis killing by human neutrophils

Interleukin-15 is a cytokine produced by a wide range of different cell types, including macrophages, in response to lipopolysaccharide or microbial infection. This cytokine may play a crucial role in the activation of phagocytic cells against pathogens, especially during innate immune response. The effects of IL-15 on human polymorphonuclear leukocyte fungicidal activity against a highly virulent Paracoccidioides brasiliensis strain were investigated. Pretreatment of human neutrophils from healthy individuals with IL-15 for IS h increased cell fungicidal activity in a dose-dependent manner. In addition, the exposure to IL-15 induced an increase in neutrophil oxidative burst as evaluated by superoxide anion and H(2)O(2) release. Catalase inhibited fungicidal activity supporting a role for H(2)O(2) in fungus killing. In contrast, IL-8 and TNF-alpha levels were not affected by IL-15 suggesting that its effects were not mediated by these cytokines. Together, these results show that IL-15 is a potent stimulant of antifungal activities in human neutrophils, at least in part by a mechanism dependent on oxidative metabolism. (c) 2007 Elsevier Ltd. All rights reserved.

Efeito do óxido nítrico inalatório associado à ventilação mecânica protetora na lesão pulmonar aguda induzida experimentalmente

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antiplatelet drugs reduce the immunoinflammatory response in a rat model of periodontal disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito do plasma rico em uréia na apoptose de neutrófilos de cães

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A novel biological activity for galectin-1: Inhibition of leukocyte-endothelial cell interactions in experimental inflammation

Galectin-1 (Gal-1), the prototype of a family of β -galactoside-binding proteins, has been shown to attenuate experimental acute and chronic inflammation. In view of the fact that endothelial cells (ECs), but not human polymorphonuclear leukocytes (PMNs), expressed Gal-1 we tested here the hypothesis that the protein could modulate leukocyte-EC interaction in inflammatory settings. In vitro, human recombinant (hr) Gal-1 inhibited PMN chemotaxis and trans-endothelial migration. These actions were specific as they were absent if Gal-1 was boiled or blocked by neutralizing antiserum. In vivo, hrGal-1 (optimum effect at 0.3 μg equivalent to 20 pmol) inhibited interleukin-1β-induced PMN recruitment into the mouse peritoneal cavity. Intravital microscopy analysis showed that leukocyte flux, but not their rolling velocity, was decreased by an anti-inflammatory dose of hrGal-1. Binding of biotinylated Gal-1 to resting and post-adherent human PMNs occurred at concentrations inhibitory in the chemotaxis and transmigration assays. In addition, the pattern of Gal-1 binding was differentially modulated by PMN or EC activation. In conclusion, these data suggest the existence of a previously unrecognized function of Gal-1, that is inhibition of leukocyte rolling and extravasation in experimental inflammation. It is possible that endogenous Gal-1 may be part of a novel anti-inflammatory loop in which the endothelium is the source of the protein and the migrating PMNs the target for its anti-inflammatory action.

Circulating leukocyte heat shock protein 70 (HSP70) and oxidative stress markers in rats after a bout of exhaustive exercise

A novel method to measure oxidative stress resulting from exhaustive exercise in rats is presented. In this new procedure we evaluated the erythrocyte antioxidant enzymes, catalase ( CAT) and glutathione reductase (GR), the plasma oxidative attack markers, reactive carbonyl derivatives (RCD) and thiobarbituric reactive substances (TBARS). Muscular tissue damage was evaluated by monitoring plasma creatine kinase (CK) and plasma taurine ( Tau) concentrations. Also, we monitored total sulphydryl groups (TSG) and uric acid (UA), and the level of the 70 kDa heat shock protein (HSP70) in leukocytes as a marker of oxidative stress. In the study we found a correspondence between erythrocyte CAT and GR activities and leukocyte HSP70 levels, principally 3 h after the acute exercise, and this suggested an integrated mechanism of antioxidant defense. The increase in levels of plasma Tau was coincident with the increasing plasma levels of CK and TBARS, principally after two hours of exercise. Thus tissue damage occurred before the expression of any anti-oxidant system markers and the monitoring of Tau, CK or TBARS may be important for the estimation of oxidative stress during exhaustive exercise. Furthermore, the integrated analyses could be of value in a clinical setting to quantify the extent of oxidative stress risk and reduce the need to perform muscle biopsies as a tool of clinical evaluation.

Antibody and blood leukocyte response in Rhipicephalus sanguineus (Latreille, 1806) tick-infested dogs and guinea pigs

The dog is considered to be the natural host of Rhipicephalus sanguineus and is unable to develop appreciable resistance even after repeated feedings. The guinea pig develops strong resistance after one infestation with adult ticks. Antibody (IgG) titres against tick salivary gland antigens (SGAs) and blood leukocyte numbers in dogs and guinea pigs undergoing experimental R. sanguineus tick infestations were measured to detect a possible correlation with susceptibility or resistance of hosts. Since infested dogs develop an immediate hypersensitivity reaction to R. sanguineus antigens, total and anti-R. sanguineus SGA IgE levels were also measured in this host species. IgG and IgE antibody levels were determined by an enzyme-linked immunosorbent assay (ELISA) along three consecutive infestations of both hosts. Most dogs and guinea pigs displayed low IgG levels against R. sanguineus SGAs, though marked differences in individual response were observed. Although dog's total serum IgE levels increased significantly after infestations, no change in the amount of anti-salivary gland IgE was detected. Total and differential blood cell counts were determined in dogs and guinea pigs during primary and secondary infestation. In dogs, a tertiary infestation and a subsequent higher infestation level were also evaluated. Infested dogs did not display any alteration in blood leukocyte counts throughout the experiment. Guinea pigs, on the other hand, developed a significant basophilia during primary infestation which increased further during secondary infestation. These data reveal similarities and differences in the reactions of resistant and non-resistant hosts to ticks. They contribute for the understanding of such host-parasite relationships and will hopefully aid in the development of immune control of ticks. (C) 2003 Elsevier B.V. All rights reserved.

Chloramphenicol restores the polymorphonuclear accumulation in carrageenin-induced pleurisy in diabetic rats

Investigou-se o efeito do succinato de cloranfenicol (30 mg/kg, a cada 12 h, durante 4 dias, IP) sobre o acúmulo de leucócitos polimorfonucleares (PMN) na pleurisia induzida pela carragenina (150 mig) em ratos (Wistar, machos, 180-230 g, n = 12) diabéticos (40 mg/kg de aloxana, IV). O antibiótico produziu aumento de 36% no número de PMN (p<0,05) migrados para a cavidade pleural de animais normais. O estado diabético provocou redução de 45% dos PMN (p<0,05) acumulados no exsudato pleural de animais não tratados com o antibiótico. Por outro lado, animais diabéticos tratados com succinato de cloranfenicol apresentaram resposta de PMN que não diferiu estatisticamente do observado em animais controle, não tratados. A contagem total e diferencial dos leucócitos circulantes realizada antes e 4 h depois da aplicação da carragenina não diferiu estatisticamente entre os grupos.

Leukocyte entry into the CNS of Leishmania chagasi naturally infected dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Zidovudine-Loaded PLA and PLA-PEG Blend Nanoparticles: Influence of Polymer Type on Phagocytic Uptake by Polymorphonuclear Cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of nonclassical molecule human leukocyte antigen-G in oral lesions

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45(51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier B.V. All rights reserved.

Chemiluminescent determination of leukocyte alkaline phosphatase: An advantageous alternative to the cytochemical assay

The determination of leukocyte alkaline phosphatasd (LAP) is used as an aid to diagnose many diseases in the laboratory. For example, it can be used to distinguish chronic myeloid leukemia (CML) from other myeloproliferative disorders (particularly myelofibrosis and polycythemia) and leukemoid reactions (LR). Traditionally, this test is performed with the use of subjective cytochemical assays that assign a score to the level of LAP. Here we present a nonsubjective, quantitative, sensitive, and inexpensive chemiluminescent technique that determines LAP based on the commercial reagent Immulite (R) (AMPPD). To validate this methodology, intact leukocytes obtained from 32 healthy subjects, nine CML patients, and nine LR patients were submitted to the optimized protocol. By measuring the light emission elicited by four concentrations of neutrophils, we were able to estimate the activity of LAP per cell (the slope of the curve obtained by linear regression). A high linear correlation was found between the chemiluminescent result (slope) and the cytochemical score. The slope for healthy individuals ranged between 0.61 and 8.49 (10(-5) mV.s/cell), with a median of 2.04 (10(-5) mV.s/cell). These results were statistically different from those of CML patients (range = 0.07-1.75, median = 0.79) and LR patients (range = 3.84-47.24, median 9.58; P < 0.05).

4-Fluoro-2-methoxyphenol, an apocynin analog with enhanced inhibitory effect on leukocyte oxidant production and phagocytosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)