Pre-pubertal bovine mammary development involves ductal and stromal tissue changes. In mice, this process is impacted by presence of innate immune cells. Whether or not such immune cells are present or involved in bovine mammary development is unknown. We studied the presence, location and changes in numbers of eosinophils, mast cells and macrophages in pre-pubertal bovine mammary tissue. Chemical stains and immunofluorescence were used to identify the cells in formalin fixed, paraffin embedded mammary tissue. The first set (ONT) included samples (n=4/week) from birth to 6 weeks of age. Another set (OVX) determined the influence of ovaries, 19 animals were intact or ovariectomized 30 days before sampling. They were 90, 120 or 150 days old at examination. The third set (EST) allowed examination of the potential influence of exogenous estrogen on innate immune cells in the mammary gland. Samples were from calves given estrogen implants (n=6) or placebo (n=4) at 56 days old, and sampled at 70 days old. We examined 20 images each of NEAR and FAR stroma from every animal. More eosinophils were observed in NEAR versus FAR in the ONT and OVX , more mast cells observed in NEAR versus FAR in ONT. More macrophages were observed in NEAR versus FAR in ONT and EST. We show, for the first time, that innate immune cells are present in prepubertal bovine mammary tissue and that abundance is related to the epithelial structure. We suggest a possible role for these cells in control of bovine mammary development. / Master of Science

Atopic dermatitis (AD) is a common skin disease that is characterized by chronic, relapsing skin inflammation and eczematous, itchy lesions. In AD, systemic and local eosinophilia and basophilia is thought to contribute to disease progression in both acute and chronic lesions. It has been previously shown that in chronic allergic inflammatory diseases, tissue eosinophilia and basophilia may in part result from eosinophil/basophil (Eo/B) progenitors trafficking from the bone marrow and maturing in tissue in response to type 2 cytokines including IL-5 and IL-3. We therefore proposed that a similar mechanism could be contributing to the pathogenesis of AD. First, we compared lesional and non-lesional AD tissue, and found approximately 10-fold higher levels of Eo/B progenitors in the lesional tissue (p<0.05). As previous research has shown an increase in Eo/B progenitors in the airways of allergic asthmatics post inhaled allergen challenge, we next examined whether Eo/B progenitors increased locally in the acute phase of AD using the intradermal allergen challenge model. Compared to intradermal diluent challenge there was an increase in Eo/B progenitors (5.5-fold), eosinophils (18-fold) and basophils (2.5-fold) 24 hours post intradermal allergen challenge (all p<0.05). These increases were consistent with findings in allergic airways. Lastly, we examined the relationship between disease severity and Eo/B progenitors in inflamed lesional (chronic) and allergen-challenged (acute) tissue. We found that Eo/B progenitors in lesional tissue positively correlated with disease severity (EASI R=0.71, p<0.05 and SCORAD R=0.65, p<0.05), while in allergen-challenged tissue a trend was seen for a positive correlation between Eo/B progenitors and disease severity (EASI R=0.48, p=0.07 and SCORAD R=0.46, p=0.09). These results highlight the potential involvement of Eo/B progenitors in the disease pathogenesis of AD. / Thesis / Master of Science (MSc) / Atopic dermatitis is a common skin disease that is characterized by chronic, relapsing skin inflammation and eczematous, itchy lesions. In other allergic diseases, a cell called the “eosinophil/basophil progenitor” contributes to the accumulation of inflammatory cells in the diseased organ. We proposed that eosinophil/basophil progenitors found in the skin may be contributing to the development of local allergic inflammation. In patients with moderate-to-severe atopic dermatitis we compared acute responses to intradermal allergen and chronic skin lesions to diluent-challenged and un-affected skin, respectively. Allergen-challenged skin had more eosinophil/basophil progenitors, mature eosinophils and basophils 24 hours’ post-challenge compared to unchallenged skin (p<0.05). Chronic skin lesions had more eosinophil/basophil progenitors than un-affected skin (p<0.05). The number of eosinophil/basophil progenitors positively correlated to disease severity as determined by EASI and SCORAD. Our results suggest that accumulation of eosinophil/basophil progenitors in skin of atopic dermatitis patients could support allergic inflammation and contribute to disease severity.

Rationale: Eosinophils are “end cell” leucocytes, associated with allergy, asthma and helminthiasis. At sites of inflammation, eosinophils may modulate immune response through expression of the extra-hepatic tryptophan-catabolising enzyme, Indoleamine 2, 3-dioxygenase (IDO). Kynurenines, products of tryptophan cleavage, induce apoptosis of T-cells, including thymocytes. Eosinophils naturally home to the thymi in mammals. Thymus is a primary lymphoid organ, where T-cells develop and undergo selection. My hypothesis is that eosinophils homing to the thymi participate in T-cell development through their expression of IDO. Methods: Immunohistochemistry revealed eosinophils in thymic tissue. Immunocytochemistry and flow cytometry were used to locate IDO protein expression in the thymus particularly in thymic eosinophils. RT-PCR and real-time PCR determined the presence of IDO mRNA in the thymus. Results: thymic eosinophils express IDO and infiltrate compartments associated with negative selection. The highest IDO transcription correlated with the influx of eosinophils and prevalence of immature thymocytes. / Experimental Medicine

No description available.

There is no doubt that eosinophils and neutrophils are important cells participating in asthma pathogenesis. The most prominent feature reflecting asthma pathogenesis is late-phase airway inflammation, which occurs a few hours after allergen inhalation. The worldwide published studies on asthma show that most attention is paid to individual, not complex, functions of neutrophils and eosinophils in the airways. Moreover, associations between peripheral blood neutrophil and eosinophil activity and infiltration of these cells in the airways during asthma have not been com¬pletely elucidated yet. There are no data about peripheral blood neutrophil and eosinophil activity during allergen-induced late-phase airway inflam¬mation in asthma patients. Therefore, the aim of this study was to evaluate peripheral blood neutrophil and eosinophil functional activity during allergen-induced late-phase airway inflammation in asthma. We found that an inhaled allergen activates peripheral blood neutrophil and eosinophil chemotaxis, phagocytosis, generation of reactive oxygen species and also reduces apoptosis during late-phase airway inflammation in asthma. Furthermore, altered peripheral blood neutrophil and eosinophil functional activity is related with airway neutrophilia and eosinophilia. Our findings provide new evidence about neutrophil and eosinophil functional activity during allergen-induced late-phase airway inflammation in asthma patients. / Mokslininkai neabejoja, jog eozinofilai ir neutrofilai yra vienos svarbiausių ląstelių, dalyvaujančių astmos patogenezėje, kurią labiausiai atspindi vėlyva kvėpavimo takų uždegimo fazė, išsivystanti praėjus kelioms valandoms po alergeno įkvėpimo. Pasaulinėje literatūroje publikuojami darbai, nagrinėja atskirus kvė¬pavimo takų neutrofilų ir eozinofilų aktyvumo pokyčius. Ypač mažai darbų apie periferinio kraujo neutrofilų ir eozinofilų funkcijas bei jų ryšį su šių ląstelių pagausėjimu kvėpavimo takuose, sergant astma. Taip pat nėra tyrimų, vertinančių periferinio kraujo uždegimo ląstelių (neutrofilų ir eozi¬nofilų) funkcijų alergeno sukeltos vėlyvos fazės kvėpavimo takų uždegimo metu. Todėl šio tyrimo tikslas buvo įvertinti periferinio kraujo neutrofilų ir eozinofilų funkcinį aktyvumą alergeno sukeltos vėlyvos fazės kvėpavimo takų uždegimo metu sergant astma. Tyrimo metu nustatėme, kad įkvėptas alergenas aktyvina periferinio kraujo neutrofilų ir eozinofilų funkcijas - chemotaksį, fagocitozę, reaktyvių deguonies formų susidarymą, degranuliaciją bei silpnina apoptozę vėlyvos fazės kvėpavimo takų uždegimo metu. O šių ląstelių aktyvumo pokyčiai yra susiję su kvėpavimo takų neutrofilija ir eozinofilija. Moksliniame darbe pateikiami rezultatai suteikia naujų duomenų apie sergančiųjų alergine astma periferinio kraujo neutrofilų ir eozinofilų funkcinių savybių ypatumus ir parodo jų pokyčius alergeno sukeltos vėlyvos fazes kvėpavimo takų uždegimo metu.

Introdução: Dispepsia funcional é uma doença de alta prevalência e grande impacto econômico e social. Sua etiologia ainda é pouco conhecida, e a literatura tem sugerido a associação do aumento do número de eosinófilos em mucosa duodenal com os sintomas dispépticos. No entanto, o tema ainda é controverso. Objetivo: Avaliar se existe associação entre contagem de eosinófilos duodenais e sintomas dispépticos. Métodos: Foram incluídos pacientes dispépticos funcionais pelos critérios de Roma III (casos) e indivíduos assintomáticos do trato gastrointestinal (controles). Os dois grupos foram pareados por idade, sexo e infecção por Helicobacter pylori (H. pylori). Eosinófilos da segunda porção duodenal foram quantificados em 5 campos de maior aumento (CMA), selecionados randomicamente em fragmentos de biópsias endoscópicas, e o valor comparado entre os grupos. Resultados: Foram incluídos 42 dispépticos funcionais e 21 controles (idade média 39,6 e 38,7 anos respectivamente); 71,4% mulheres e 61,9% H. pylori positivos em cada grupo. Casos e controles apresentaram semelhante contagem de eosinófilos/CMA na biópsia duodenal, mediana 11,9 e 12,6 respectivamente (P=0,194). No grupo de casos a contagem de eosinófilos foi maior entre os portadores de H. pylori do que nos indivíduos não infectados (mediana 13,6 versus 6,1 P<0,001); no entanto foi semelhante no grupo de controles (mediana 12,6 versus 15,7 P=0,8). Conclusões: Não foi demonstrada diferença de contagem de eosinófilos duodenais entre dispépticos funcionais e controles. Entretanto, parece haver interação com infiltrado eosinofílico e sintomas no subgrupo de casos infectados pelo H. pylori. / Introduction: Functional dyspepsia is a highly prevalent disease with major economic and social impact. Its etiology is still poorly understood, and it has been suggested the association of increased numbers of eosinophils in duodenal mucosa with dyspeptic symptoms. However, this issue is still controversial. Objective: To determine if there is association between duodenal eosinophilia and dyspeptic symptoms. Methods: Functional dyspeptic patients according to the Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were included. Groups were matched by age, sex and infection with Helicobacter pylori (H. pylori). Eosinophils in the second duodenal portion were counted in five high-power fields (HPF), randomly selected in endoscopic biopsies and the value was compared between groups. Results: 42 functional dyspeptic patients and 21 controls (mean age 39.6 and 38.7 years old, respectively) were included; 71.4% were women and 61.9% were positive for H. pylori in each group. Cases and controls had similar eosinophil counts/HPF in the duodenal biopsy: median 11.9 and 12.6 respectively (P = 0.194). In the case group the eosinophil count was higher in H. pylori carriers than in noncarriers (median 13,6 versus 6,1 P<0,001); however this count was similar in the control group (median 12,6 versus 15,7 P=0,8). Conclusions: No difference was found in duodenal eosinophil count between functional dyspeptic patients and controls. However, there seems to be an interaction between eosinophilic infiltrate and symptoms in the subgroup of H. pylori-infected cases.

Made available in DSpace on 2016-08-17T18:39:45Z (GMT). No. of bitstreams: 1 4808.pdf: 1657962 bytes, checksum: abb30e9c4dc48bb4625a333ce6600cb8 (MD5) Previous issue date: 2012-02-28 / Eosinophils are a hematopoietic cell originated from precursor cells found in bone marrow, whose differentiation and proliferation is regulated by cytokines such as GM-CSF, IL-3 and IL-5. When activated, eosinophils are capable of phagocytosis of small particles and bacteria, but their main form of activity in the inflammatory process is the release of toxic proteins, cytokines, enzymes, lipid mediators and reactive oxygen products. The increase in eosinophil is an important feature in many diseases such as allergy and parasitic infections. Provided APC (Antigen-Presenting Cells), eosinophils are considered similar to the CD (Dendritic Cells) in its potential to activate naïve T cells and may have potential as efficient as the CD in stimulating lung T cells in the upper airways in the model inflammation. The APC are defined by being able to take, processing and presenting antigen such as CD, macrophages, B lymphocytes and possibly eosinophils. The surface expression of APC is characterized by coestimatórias molecules CD80 (B7-1) and CD86 (B7-2) and also by MHCII. The proposed model for this evaluation was to Visceral Larva Migrans syndrome (VLMS) caused by Toxocara canis, one of the most frequent helminth in young dogs. One of the main consequences of this infection is the marked increase in circulating and tissue eosinophils. Eosinophilia has been associated with parasitic diseases particularly when the parasite invades or promotes tissue damage at mucosal surfaces In the present study we evaluated the expression of MHC II and CD80 and CD86 molecules coestimulatórias in eosinophils in VLMS. Our results showed that the molecules studied were expressed in eosinophils in the blood of mice infected with Toxocara canis compared with the control group. Correlating an intense eosinophil still during the course of the disease with increased IL-5 in the infected group. Suggests that during the course of Toxocara canis, eosinophils can exhibit behavior of an APC, increasing the expression of MHCII molecules coestimulatorias and possibily amplifyng the immune response in this model. / O eosinófilo é uma célula hematopoiética, originada a partir de células precursoras presentes na medula óssea, cuja diferenciação e proliferação são reguladas por citocinas como GMCSF, IL-3 e IL-5. Quando ativados, os eosinófilos são capazes de realizar fagocitose de pequenas partículas e bactérias, mas sua principal forma de atuação no processo inflamatório consiste na liberação de proteínas tóxicas, citocinas, enzimas, mediadores lipídicos e produtos reativos de oxigênio. O aumento no número de eosinófilos é uma característica importante em diversas doenças como a alergia e as infecções parasitárias. Na condição de APC (Células Apresentadoras de Antígenos), os eosinófilos são considerados similares as CD (Células Dendríticas) em seu potencial para ativar células T naïve, podendo ter potencial tão eficiente quanto as CD pulmonares em estimular células T nas vias aéreas superiores no modelo da inflamação. As APC são definidas por serem capazes de ingerir, processar e apresentar o antígeno como: CD, macrófagos, linfócitos B e possivelmente os eosinófilos. A expressão na superfície da APC é caracterizada por moléculas coestimatórias CD80 (B7-1) e CD86 (B7-2) e ainda pelo MHCII. O modelo proposto para esta avaliação foi a Síndrome da Larva Migrans Visceral (SLMV) causada pelo Toxocara canis, um dos helmintos mais freqüentes em cães jovens. Uma das principais consequências desta infecção é o aumento marcante de eosinófilos circulantes e teciduais. A eosinofilia tem sido associada com doenças parasitárias particularmente quando o parasita invade os tecidos ou promove danos na superfície das mucosas. No presente estudo avaliamos a expressão de MHC II e moléculas coestimulatórias CD80 e CD86 em eosinófilos na SLMV. Nossos resultados mostraram que as moléculas analisadas foram expressas em eosinófilos no sangue de camundongos infectados com Toxocara canis quando comparado com o grupo controle. Correlacionando ainda uma intensa eosinofilia durante o curso da doença com o aumento de IL-5 no grupo infectado. Sugere que, durante o curso da infecção pelo Toxocara canis, eosinófilos podem apresentar comportamento de uma APC, aumentando a expressão de moléculas coestimulatórias e MHCII e possivelmente amplificando a resposta imune nesse modelo.

Introdução: Dispepsia funcional é uma doença de alta prevalência e grande impacto econômico e social. Sua etiologia ainda é pouco conhecida, e a literatura tem sugerido a associação do aumento do número de eosinófilos em mucosa duodenal com os sintomas dispépticos. No entanto, o tema ainda é controverso. Objetivo: Avaliar se existe associação entre contagem de eosinófilos duodenais e sintomas dispépticos. Métodos: Foram incluídos pacientes dispépticos funcionais pelos critérios de Roma III (casos) e indivíduos assintomáticos do trato gastrointestinal (controles). Os dois grupos foram pareados por idade, sexo e infecção por Helicobacter pylori (H. pylori). Eosinófilos da segunda porção duodenal foram quantificados em 5 campos de maior aumento (CMA), selecionados randomicamente em fragmentos de biópsias endoscópicas, e o valor comparado entre os grupos. Resultados: Foram incluídos 42 dispépticos funcionais e 21 controles (idade média 39,6 e 38,7 anos respectivamente); 71,4% mulheres e 61,9% H. pylori positivos em cada grupo. Casos e controles apresentaram semelhante contagem de eosinófilos/CMA na biópsia duodenal, mediana 11,9 e 12,6 respectivamente (P=0,194). No grupo de casos a contagem de eosinófilos foi maior entre os portadores de H. pylori do que nos indivíduos não infectados (mediana 13,6 versus 6,1 P<0,001); no entanto foi semelhante no grupo de controles (mediana 12,6 versus 15,7 P=0,8). Conclusões: Não foi demonstrada diferença de contagem de eosinófilos duodenais entre dispépticos funcionais e controles. Entretanto, parece haver interação com infiltrado eosinofílico e sintomas no subgrupo de casos infectados pelo H. pylori. / Introduction: Functional dyspepsia is a highly prevalent disease with major economic and social impact. Its etiology is still poorly understood, and it has been suggested the association of increased numbers of eosinophils in duodenal mucosa with dyspeptic symptoms. However, this issue is still controversial. Objective: To determine if there is association between duodenal eosinophilia and dyspeptic symptoms. Methods: Functional dyspeptic patients according to the Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were included. Groups were matched by age, sex and infection with Helicobacter pylori (H. pylori). Eosinophils in the second duodenal portion were counted in five high-power fields (HPF), randomly selected in endoscopic biopsies and the value was compared between groups. Results: 42 functional dyspeptic patients and 21 controls (mean age 39.6 and 38.7 years old, respectively) were included; 71.4% were women and 61.9% were positive for H. pylori in each group. Cases and controls had similar eosinophil counts/HPF in the duodenal biopsy: median 11.9 and 12.6 respectively (P = 0.194). In the case group the eosinophil count was higher in H. pylori carriers than in noncarriers (median 13,6 versus 6,1 P<0,001); however this count was similar in the control group (median 12,6 versus 15,7 P=0,8). Conclusions: No difference was found in duodenal eosinophil count between functional dyspeptic patients and controls. However, there seems to be an interaction between eosinophilic infiltrate and symptoms in the subgroup of H. pylori-infected cases.

Introdução: Dispepsia funcional é uma doença de alta prevalência e grande impacto econômico e social. Sua etiologia ainda é pouco conhecida, e a literatura tem sugerido a associação do aumento do número de eosinófilos em mucosa duodenal com os sintomas dispépticos. No entanto, o tema ainda é controverso. Objetivo: Avaliar se existe associação entre contagem de eosinófilos duodenais e sintomas dispépticos. Métodos: Foram incluídos pacientes dispépticos funcionais pelos critérios de Roma III (casos) e indivíduos assintomáticos do trato gastrointestinal (controles). Os dois grupos foram pareados por idade, sexo e infecção por Helicobacter pylori (H. pylori). Eosinófilos da segunda porção duodenal foram quantificados em 5 campos de maior aumento (CMA), selecionados randomicamente em fragmentos de biópsias endoscópicas, e o valor comparado entre os grupos. Resultados: Foram incluídos 42 dispépticos funcionais e 21 controles (idade média 39,6 e 38,7 anos respectivamente); 71,4% mulheres e 61,9% H. pylori positivos em cada grupo. Casos e controles apresentaram semelhante contagem de eosinófilos/CMA na biópsia duodenal, mediana 11,9 e 12,6 respectivamente (P=0,194). No grupo de casos a contagem de eosinófilos foi maior entre os portadores de H. pylori do que nos indivíduos não infectados (mediana 13,6 versus 6,1 P<0,001); no entanto foi semelhante no grupo de controles (mediana 12,6 versus 15,7 P=0,8). Conclusões: Não foi demonstrada diferença de contagem de eosinófilos duodenais entre dispépticos funcionais e controles. Entretanto, parece haver interação com infiltrado eosinofílico e sintomas no subgrupo de casos infectados pelo H. pylori. / Introduction: Functional dyspepsia is a highly prevalent disease with major economic and social impact. Its etiology is still poorly understood, and it has been suggested the association of increased numbers of eosinophils in duodenal mucosa with dyspeptic symptoms. However, this issue is still controversial. Objective: To determine if there is association between duodenal eosinophilia and dyspeptic symptoms. Methods: Functional dyspeptic patients according to the Rome III criteria (cases) and individuals without gastrointestinal symptoms (controls) were included. Groups were matched by age, sex and infection with Helicobacter pylori (H. pylori). Eosinophils in the second duodenal portion were counted in five high-power fields (HPF), randomly selected in endoscopic biopsies and the value was compared between groups. Results: 42 functional dyspeptic patients and 21 controls (mean age 39.6 and 38.7 years old, respectively) were included; 71.4% were women and 61.9% were positive for H. pylori in each group. Cases and controls had similar eosinophil counts/HPF in the duodenal biopsy: median 11.9 and 12.6 respectively (P = 0.194). In the case group the eosinophil count was higher in H. pylori carriers than in noncarriers (median 13,6 versus 6,1 P<0,001); however this count was similar in the control group (median 12,6 versus 15,7 P=0,8). Conclusions: No difference was found in duodenal eosinophil count between functional dyspeptic patients and controls. However, there seems to be an interaction between eosinophilic infiltrate and symptoms in the subgroup of H. pylori-infected cases.

Orientador: Heloísa Helena de Araújo Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-17T04:19:45Z (GMT). No. of bitstreams: 1 Pelaquini_EdmarHenrique_M.pdf: 18418086 bytes, checksum: fa003dada60c0eb4043e3908a67d256b (MD5) Previous issue date: 2010 / Resumo: O objetivo deste trabalho foi verificar o efeito do tratamento com 1400W, inibidor seletivo da NOS induzível (iNOS), na adesão in vitro a VCAM-1 e ICAM-1 e na expressão das selectinas VLA-4, Mac-1 e LFA-1 nos eosinófilos da medula óssea e do sangue periférico. A produção das citocinas sintetizadas pelos linfócitos T, Th1 e Th2, também foi avaliada nos homogenatos dos pulmões. Verificamos que o conteúdo de eosinófilos estava aumentado nos pulmões dos camundongos não tratados (controles) a partir de 48h após o desafio com OVA. O tratamento dos camundongos alérgicos com 1400W causou redução no infiltrado de eosinófilos somente em 48h. O tratamento com 1400W aumentou a adesão in vitro dos eosinófilos obtidos da medula óssea a ICAM-1 em 24h-48h, enquanto que a adesividade a VCAM-1 estava diminuída em 48h. Nos eosinófilos do sangue, o 1400W diminuiu a adesão a VCAM-1 em 24h-48h. Na análise por citometria de fluxo não foram observadas alterações na expressão do CD11a sobre os eosinófilos da medula óssea ou do sangue periférico obtidos de ambos os grupos. Um aumento da expressão do CD11b nos eosinófilos da medula óssea dos controles foi verificada em 48h, enquanto que, neste período, CD11b e CD49d estavam diminuídas nos eosinófilos do sangue. O tratamento com 1400W aumentou a expressão do CD11b dos eosinófilos da medula óssea em 24h e 48h e provocou efeitos contrários nas células do sangue ao diminuir sua expressão em 24h e aumentar em 48h. Do mesmo modo, efeitos inversos do 1400W sobre a CD49d foram detectados no sangue quando reduziu sua expressão em 24h, aumentando-a em 48h. O desafio com OVA provocou em 24h aumento nos níveis de todas citocinas nos pulmões dos controles. Não foram observadas outras variações significativas nos níveis de IFN-y e TNF-a em nenhum dos grupos. A eotaxina mostrou pico de produção em 48h-72 horas nos animais controles, quando o tratamento com 1400W reduziu sua síntese nos pulmões. A IL-4, IL-5, IL-10 e IL-13 estavam aumentadas nos camundongos controles em 24h, sendo que picos de IL-4 e IL-13 foram detectados em 24h e 48h, respectivamente. Níveis elevados de IL-5 foram observados em 24-48h. O tratamento com 1400W reduziu os níveis de IL-4 no pulmão em 24h-48h após o desafio com OVA, assim como os de IL-5 em 48h e de IL-13 em 48h-72h. Somente em 72h o 1400W diminuiu o nível da IL-10 no pulmão. Em conclusão, nossos resultados sugerem que o envolvimento do NO na modulação da secreção de citocinas derivadas dos linfócitos Th2 e da eotaxina nos pulmões, bem como na expressão das moléculas de adesão nos eosinófilos da medula óssea e do sangue periférico, pode influenciar a migração celular para os pulmões dos camundongos alérgicos. O NO produz um efeito temporal na expressão/função do Mac-1, sugerindo ser esta a principal molécula de adesão envolvida no efluxo dos eosinófilos da medula óssea em 24h, enquanto o Mac-1 e o VLA-4 estão envolvidos na mobilização dos eosinófilos do sangue periférico para o pulmão em 48h após o desafio antigênico. / Abstract: The aim of this study was investigated the effectiveness of treatment with 1400W, a selective inhibitor of inducible NOS (iNOS) in in vitro adhesion to VCAM-1 and ICAM-1 and VLA-4, Mac-1 and LFA-1 expression in eosinophils from bone marrow and peripheral blood. The cytokines synthesized by T lymphocytes, Th1 and Th2 cells, was evaluated in lungs homogenates. As a result we found that the eosinophils were increased from 48h after OVA challenge in lungs of untreated mice (controls). Treatment of allergic mice with 1400W caused a reduction in eosinophils infiltration only after 48h. 1400W increased between 24-48h the in vitro adhesion of bone marrow eosinophils to ICAM-1, whereas adhesion to VCAM-1 was decreased after 48h. In the blood eosinophils, 1400W decreased adhesion to VCAM-1 between 24-48h. Flow cytometric analysis showed no significant changes in the expression of CD11a on bone marrow and peripheral blood eosinophils obtained from both groups. An increased expression of CD11b on bone marrow eosinophils of controls was observed after 48h, while on that period, CD11b and CD49d expression were reduced in blood eosinophils. In the bone marrow eosinophils, treatment with 1400W increased CD11b expression in both 24h and 48h, but in the blood cells caused adverse effects by decreasing expression after 24h and increase after 48h. Similarly, the opposite 1400W effect was detected in the blood cells when CD49d expression had been reduced after 24h and increased after 48h. The OVA challenge resulted in increasing the levels of all cytokines in the control lungs after 24h. There were no other significant variations in the IFN-y and TNF-a levels in both groups. In control animals, the eotaxin showed peak production between 48-72h, while 1400W treatment reduced its synthesis in the lungs. IL-4, IL-5, IL-10 and IL-13 were increased in control mice after 24 hours, with peaks of IL-4 and IL-13 were detected after 24h and 48h, respectively. Elevated levels of IL-5 were observed between 24-48h. Treatment with 1400W reduced the levels of IL-4 in lung between 24h-48h after OVA challenge, as well as IL-5 in 48 hours and IL-13 in 48h-72h. Only after 72h 1400W decreased the level of IL-10 in the lung. In conclusion, our results suggest that the involvement of NO in modulating the secretion of cytokines derived from Th2 lymphocytes and eotaxin in the lungs, as well as in the adhesion molecules expression in bone marrow and peripheral blood eosinophils may influence cell migration to the lungs of allergic mice. NO produces a temporal effect on the expression / function of Mac-1, suggesting that the main adhesion molecule involved in the efflux of bone marrow eosinophils after 24h, while Mac-1 and VLA-4 were involved in the mobilization of peripheral blood eosinophils to the lungs in 48 h after antigen challenge. / Mestrado / Mestre em Farmacologia