Thèse (M.Sc.) -- Université Laval, 1997. / Bibliogr.: f. 75-91. Publié aussi en version électronique.

Εισαγωγή: Η κλινική πορεία της οξείας παγκρεατίτιδας (ΟΠ) αντανακλά την ένταση της φλεγμονώδους αντίδρασης και ταξινομείται σε ήπια ΟΠ (ΗΟΠ) και βαριά ΟΠ (ΒΟΠ). Η έκφραση του γονιδίου της χημειοτακτικής πρωτεΐνης των μονοκυττάρων (MCP-1) επηρεάζεται από έναν A/G πολυμορφισμό (-2518) με το G αλληλόμορφο να αυξάνει την παραγωγή της MCP-1. Παχύσαρκοι ασθενείς εμφανίζουν αυξημένο κίνδυνο για επιπλοκές από ΟΠ. Το σύστημα APACHE-O έχει προταθεί ότι βελτιώνει την ακρίβεια του συστήματος APACHE-ΙΙ στην πρόγνωση της ανάπτυξης ΒΟΠ. Στόχοι: 1) Να διευκρινίσουμε αν ο πολυμορφισμός στο γονίδιο της MCP-1 στη θέση -2518 επηρεάζει την βαρύτητα της ΟΠ, 2) αν το σύστημα APACHE-O βελτιώνει την προγνωστική αξία του συστήματος APACHE-ΙΙ και 3) να διερευνήσουμε την υπόθεση ότι οι παχύσαρκοι ασθενείς βρίσκονται σε αυξημένο κίνδυνο για την ανάπτυξη ΒΟΠ λόγω της μεγαλύτερης φλεγμονώδους απόκρισης που παρουσιάζουν στην παγκρεατική προσβολή. Μέθοδοι: Μελετήθηκαν 102 ασθενείς με ΟΠ και 116 άτομα αποτέλεσαν την ομάδα των υγιών μαρτύρων. Ο A/G γονότυπος της MCP-1 ανιχνεύθηκε με την μέθοδο της αλυσιδωτής αντίδρασης της πολυμεράσης και με προσδιορισμό της αλληλουχίας του DNA. Τα επίπεδα της MCP-1 στον ορό μετρήθηκαν με φθορίζουσα ανοσολογική μέθοδο. Υπολογίσθηκαν οι καμπύλες ROC των συστημάτων APACHE-II και APACHE-O. Η παχυσαρκία και άλλες κλινικές παράμετροι εκτιμήθηκαν ως παράγοντες κινδύνου για την ανάπτυξη ΒΟΠ με τη χρήση ανάλυσης λογισμικής παλινδρόμησης. Συγκρίναμε τα επίπεδα των IL-6, MCP-1 και CRP στον ορό και των κριτηρίων του Ranson σε παχύσαρκους και μη-παχύσαρκους ασθενείς με ΟΠ. Αποτελέσματα: 19 ασθενείς ανέπτυξαν ανεπάρκεια οργάνων και ταξινομήθηκαν ως ΒΟΠ. Οι ασθενείς με ΒΟΠ βρέθηκαν να έχουν σημαντικά υψηλότερο ποσοστό του G αλληλομόρφου (86%) σε σχέση με τους ασθενείς με ΗΟΠ (46%) (p<0,007). Οι ασθενείς με ΒΟΠ είχαν επίσης υψηλότερα επίπεδα της MCP-1 στον ορό σε σχέση με τους ασθενείς με ΗΟΠ (p=0,002). Το 28% των ασθενών ήταν παχύσαρκοι (BMI >30). Τα συστήματα APACHE-O (AUC: 0,895) και APACHE-ΙΙ (AUC: 0,893) έδειξαν παρόμοια ακρίβεια στην πρόγνωση της ανάπτυξης ΒΟΠ. Η παχυσαρκία βρέθηκε να αποτελεί παράγοντα κινδύνου για την ανάπτυξη ΒΟΠ (OR: 2,8, p=0,048) και θνητότητας (OR: 11,2, p=0,022). Τα επίπεδα της CRP (p=0,0001) και τα κριτήρια Ranson (p=0,021) βρέθηκαν σημαντικά υψηλότερα στους παχύσαρκους ασθενείς. Τα επίπεδα των IL-6 και MCP-1 βρέθηκαν υψηλότερα στους παχύσαρκους ασθενείς, χωρίς όμως να είναι στατιστικώς σημαντικά. Συμπεράσματα: Το -2518 G αλληλόμορφο της MCP-1 αποτελεί παράγοντα κινδύνου για την ανάπτυξη ΒΟΠ. Τα επίπεδα της MCP-1 δείχνουν να αποτελούν ακριβή προγνωστικό δείκτη για την ανάπτυξη ΒΟΠ και θανάτου. Η παχυσαρκία αποτελεί επίσης ανεξάρτητο παράγοντα κινδύνου για την ανάπτυξη ΒΟΠ. Το σύστημα APACHE-O κατά την εισαγωγή των ασθενών δεν είναι πιο ακριβές από το σύστημα APACHE-ΙΙ. Τα αποτελέσματα της μελέτης μας προτείνουν ότι η παχυσαρκία αυξάνει την βαρύτητα της ΟΠ λόγω της μεγαλύτερης ανοσολογικής απόκρισης στην παγκρεατική προσβολή. / Background: Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Monocyte chemotactic protein-1 (MCP-1) gene expression is altered by an A/G polymorphism (-2518), with the G allele increasing MCP-1 production. Obese patients appear to be at risk for complications of AP. APACHE-O score has been suggested to improve APACHE-II accuracy in predicting severe outcome in AP. Aims: Τo determine whether: 1) the MCP-1 −2518 A/G polymorphism affects the severity of AP, 2) if APACHE-O score adds any predictive value to APACHE-II score and 3) to test the hypothesis that obese patients are at increased risk of SAP because of a more intense inflammatory response to pancreatic injury. Methods: 102 consecutive AP patients and 116 controls were evaluated. The A/G genotype was evaluated by polymerase chain reaction amplification and DNA sequencing. MCP-1 serum levels were quantified using a fluorescence bead-based immunoassay. Receiver operating curves (ROC) for prediction of SAP were calculated using admission APACHE-II and APACHE-O scores. Binary logistic regression was performed to assess if obesity is a risk for SAP and to determine the clinical factors associated with severe disease. Serum levels of IL-6, MCP-1 and CRP as well as Ranson’s scores were compared between obese and non-obese patients. Results: Nineteen patients developed organ dysfunction and were classified as SAP. Patients with SAP had a significantly greater proportion of the G allele (86%) than did MAP patients (46%) (p<0.007). As predicted by the genotype, the serum MCP-1 levels were significantly higher in the SAP patients when compared with the MAP patients (p=0.002). Using a body mass index (BMI) >30, 28% of the subjects were obese. Admission APACHE-O (Area under the curve AUC: 0.895) and APACHE-II (AUC: 0.893) showed similar accuracy in predicting severe outcome. BMI>30 was identified as a significant risk for SAP (OR: 2.8, p=0.048) and mortality (OR: 11.2, p=0.022). CRP levels were significantly higher in obese AP patients (p=0.0001) as well as Ranson’s score (p=0.021). IL-6 and MCP-1 levels were higher in obese patients but did not reach statistical significance. Conclusions: MCP-1 −2518 G allele is a risk factor for severe AP. MCP-1 serum levels, measured early in the course of AP, appear to be an accurate predictor of severity of acute pancreatitis and death. Obesity is an independent risk for severe acute pancreatitis. Admission APACHE-O score is not more accurate than APACHE-II score. Our study results suggest that obesity increases the severity of AP by amplifying the immune response to injury.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O envolvimento renal na esquistossomose mansoni à raramente descrito e pode ser caracterizada principalmente por alteraÃÃes glomerulares, podendo permanecer assintomÃtica, daà a importÃncia de biomarcadores que possam detectar precocemente alteraÃÃes da funÃÃo renal. O objetivo foi caracterizar as alteraÃÃes renais em pacientes portadores de esquistossomose mansoni, antes e apÃs tratamento na fase intestinal, procedentes de uma Ãrea de baixa endemicidade no Estado do CearÃ. Trata-se de um estudo transversal, de carÃter avaliativo e de natureza quantitativa e intervencionista, incluindo 85 pacientes com diagnÃstico parasitolÃgico (Kato-Katz) confirmado de esquistossomose mansoni. Os pacientes foram divididos em trÃs grupos: Grupo I (G-I) - grupo controle com 24 indivÃduos nÃo infectados; Grupo II (G-II) - grupo com 30 indivÃduos infectados por S. mansoni e Grupo III (G-III) - grupo com 31 indivÃduos infectados por S. mansoni, tratados e avaliados apÃs o tratamento. A funÃÃo renal foi avaliada atravÃs de marcadores renais tubular e glomerular, incluindo dosagem do pH urinÃrio, estimativa da fraÃÃo de excreÃÃo dos eletrÃlitos (FE), estimativa do ritmo de filtraÃÃo glomerular (eRFG), albumina urinÃria e MCP-1/CCL2 urinÃrio (proteÃna quimiotÃtica de monÃcitos-1). Dados do presente estudo mostram que a maioria dos indivÃduos estavam dentro da faixa etÃria em torno de 23,2 &#61617; 13 anos, sendo 39 (45,88%) homens e 46 (54,11%) mulheres. Quando os marcadores renais tubulares foram analisados verificou-se que nÃo houve diferenÃa entre os grupos. Com relaÃÃo aos marcadores renais glomerulares foi observado que MCP-1 foi o Ãnico que apresentou diferenÃa, sendo maior no G-II (178  97pg/mcg-Cr) e no G-III (175  87pg/mcg-Cr), quando comparado com o G-I (123  48pg/mcg-Cr), p=0,009 e p=0,007, respectivamente. NÃo houve diferenÃa quando os grupos G-II e G-III (p=0,892) foram comparados. Apesar da albumina urinÃria nÃo ter apresentado diferenÃa entre os trÃs grupos, ela correlacionou-se com MCP-1 (r=0,463; p=0,01). Em suma foi observado um aumento significativo dos nÃveis urinÃrios de MCP-1 nos pacientes com esquistossomose mansoni. Como esta proteÃna desempenha um importante papel no recrutamento de monÃcitos para os sÃtios de lesÃes e infecÃÃes, o seu aumento na urina sugere que hà uma inflamaÃÃo renal e isso nÃo se reverteu apÃs o tratamento desta doenÃa. / Renal involvement in schistosomiasis is rarely reported and can be characterized mainly by glomerular and may remain asymptomatic, hence the importance of biomarkers that can detect early changes in renal function. The objective was to characterize renal changes in patients with schistosomiasis mansoni before and after treatment in the intestinal phase, coming from an area of low endemicity in the state of CearÃ. This is a cross-sectional study of character evaluation, quantitative and interventionist, including 85 patients with parasitological (Kato-Katz) confirmed schistosomiasis. Patients were divided into three groups: Group I (GI) - control group of 24 uninfected individuals, Group II (G-II) - a group of 30 individuals infected with S. mansoni and Group III (G-III) - group with 31 individuals infected with S. mansoni, processed and evaluated after treatment. Renal function was assessed by renal tubular and glomerular markers, including measurement of urinary pH, estimation of fractional excretion of electrolytes (FE), estimated glomerular filtration rate (eGFR), urinary albumin and urinary MCP-1/CCL2 ( Monocyte chemoattractant protein-1). Data from this study show that most subjects were within the age range around 23,2 Â13 years, 39 (45,88%) men and 46 (54,11%) women. When the renal tubular markers were analyzed it was found that there was no difference between groups. With respect to renal glomerular markers was observed that MCP-1 was the only one that was different, being higher in G-II (178  97pg/mcg-Cr) and G-III (175  87pg/mcg-Cr) when compared with the GI (123  48pg/mcg-Cr), p = 0,009 and p = 0,007, respectively. There was no difference among the groups G-G-II and III (p = 0,892) were compared. Although the albumin excretion did not provide a difference between the three groups, it was correlated with MCP-1 (r= 0,463, p= 0.01). In short there was a significant increase in urinary levels of MCP-1 in patients with schistosomiasis. As this protein plays an important role in the recruitment of monocytes to sites of injury and infection, its increase in urine suggests that there is an inflammation of the kidneys and this is not reversed after treatment of this disease.

La inflamació s’ha considerat tradicionalment com un mecanisme de defensa, molt lligat a la supervivència de l’espècie, per la seva capacitat de combatre les infeccions o restaurar el dany produït. No obstant, un estat d’inflamació crònic produeix un efecte totalment contrari, que s’associa a un mal funcionament de teixits i òrgans. L’objectiu d’aquest treball és l’estudi de la proteïna quimioatraient de monòcits-1 (MCP-1), una proteïna descrita per la seva funció en l’atracció de monòcits a la lesió arterioscleròtica, i que pot tenir un paper rellevant en el metabolisme. Els resultats mostren que MCP-1 està implicada en el control del metabolisme dels lípids i de la glucosa, i que l’expressió hepàtica de MCP-1 està sobre-expressada per la dieta i que contribueix al desenvolupament i progressió de l’esteatosi hepàtica en el model LDLr-/-. Precisament, l’últim treball demostra que l’estudi dels canvis metabolòmics en el teixit hepàtic ens pot ajudar a entendre aquesta patologia / Inflammation has been traditionally regarded as a defense mechanism, closely linked to the survival of the species for their ability to fight infections or restore the damage. However, a state of chronic inflammation produced a completely opposite effect, which is associated with tissue and organ malfunction. The aim of this work is the study of monocyte chemoattractant protein-1 (MCP-1), a protein described by its role in attracting monocytes to atherosclerotic lesions, which may also play an important role in metabolism. The results show that MCP-1 is involved in the control of lipids and glucose metabolism. Hepatic MCP-1 is over-expressed by diet and contributes to the development and progression of fatty liver disease (NASH) in LDLr-/- model. Indeed, the latest study shows that metabolomic changes in the liver can help us to understand the NASH progression.

Thèse (M.Sc.)--Université Laval, 2003. / Bibliogr.: f. 51-56. Publié aussi en version électronique.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / IntroduÃÃo: As lesÃes renais na hansenÃase tem grande importÃncia, pois podem evoluir para uma doenÃa renal de etiologia glomerular (glomerulonefrites, amiloidose) ou tubulointersticial. Objetivo: Investigar disfunÃÃes renais em pacientes com hansenÃase utilizando marcadores tradicionais de funÃÃo renal e a ProteÃna QuimiotÃtica de MonÃcitos-1 (MCP-1) urinÃria. PopulaÃÃo e Metodologia: Foi realizado estudo transversal e prospectivo de 44 pacientes com hansenÃase em todas as formas clÃnicas, antes do inÃcio do tratamento, sem estado reacional e sem outras nefropatias. Os pacientes foram acompanhados em centros pÃblicos de saÃde em Fortaleza, CearÃ, Brasil entre agosto de 2012 e agosto de 2013. O estudo foi aprovado pelo Comità de Ãtica em Pesquisa do Hospital UniversitÃrio Walter CantÃdio da Universidade Federal do Cearà (No: 267.426). Os pacientes foram comparados com um grupo controle composto por 15 indivÃduos sadios. Foi calculada a fraÃÃo de excreÃÃo de eletrÃlitos, estimada a taxa de filtraÃÃo glomerular (TFG), proteinÃria e microalbuminÃria. O estresse oxidativo urinÃrio foi quantificado pelo MalonaldeÃdo (MDA) urinÃrio e o MCP-1 urinÃrio foi quantificado atravÃs da tÃcnica do ELISA sanduÃche. Os valores foram normalizados pela creatinina urinÃria. Resultados: NÃo houve diferenÃa significativa entre a idade, sexo, peso corporal e pressÃo arterial entre os grupos. A idade mÃdia dos pacientes foi de 36Â10 anos, sendo 61 % do gÃnero masculino. O tempo de doenÃa variou de um mÃs a 8 anos, com mÃdia de 17 meses. A baciloscopia foi positiva em 26 pacientes (59,1%) e negativa em 18 (40,9%). Quanto à classificaÃÃo: 14 pacientes (31,8%) eram do pÃlo tuberculÃide (TT/DT), 19 (43,2%) eram dimorfos (DD) e 11 (25%) eram do pÃlo virchowiano (DV/VV). As provas de funÃÃo renal nÃo diferiram (p>0,05), com exceÃÃo da proteinÃria. Os pacientes com hansenÃase tiveram nÃveis elevados de proteinÃria (97,6Â69,2 vs 6,5Â4,3 mg/g-Cr, p<0,001) do MDA urinÃrio (1,77Â1,31 vs 1,27Â0,66 mmol/g-Cr, p=0,0372) e do MCP-1 urinÃrio (101Â79,8 vs 34,5Â14,9 mg/g-Cr, p=0,006) em relaÃÃo ao grupo controle respectivamente. O MCP-1 urinÃrio esteve maior nos pacientes multibacilares em relaÃÃo aos paucibacilares (122,1Â91,9 vs 72Â46,1 mg/g-Cr, p=0,023), respectivamente e se correlacionou positivamente com a baciloscopia (r=0,104; p=0,035), com a albuminÃria (r=0,171; p=0,006) e com o MDA urinÃrio (r=0,205; p=0,002). ConclusÃo: Em pacientes com hansenÃase sem doenÃa renal clÃnica, o MCP-1 urinÃrio esteve aumentado sobretudo no pÃlo virchowiano, e se associou com marcadores de progressÃo de lesÃo renal, apresentando grande utilidade como preditor de disfunÃÃo renal. / Introduction: Leprosy patients can present with kidney disease from glomerular (glomerulonephritis, amyloidosis) or tubule-intertitial etiology. Aims: To evaluate renal abnormalities in leprosy patients through traditional markers of renal disease and Monocyte Chemotactic Protein-1 (MCP-1). Methods: This is a cross-sectional study of 44 patients with clinical and laboratory diagnosis of leprosy and with no previous anti-mycobacterium treatment and reaction episode. Patients were recruited in public health centres in Fortaleza, Ceara, Brazil between August 2012 and August 2013. The protocol of this study was approved by the Ethical Comitee of the Walter Cantidio University Hospital, Federal University of Ceara, Brazil (N 267.426). Also, a group of 15 healthy subjects were included as a control group. Glomerular filtration rate (GFR), protein excretion, microalbuminuria and Urinary oxidative stress (malondialdehyde-MDA) were estimated. Urinary MCP-1 was determined by sandwich enzyme-linked immunosorbent assay. All urine measurements were normalized by urinary creatinine concentration. Results: Age and gender were similar between leprosy patients and control groups. Patientsâ average age was 36Â10 years, and 61% were male. Time from symptoms to leprosy diagnosis varied from one month to 8 years, with a median time of 17 months. Twenty-six patients had skin smear-positive test (59,1%) and 18 were negative (40,1%). Clinically, there were 14 (31,8%) tuberculoid polar form (TT/BT), 19 (43,2%) boderline (BB) and 11 (25%) lepromatous polar form (LL/BL). Regarding renal function, no patient had chronic kidney disease. Leprosy patients had a higher urine protein excretion (97,6Â69,2 vs 6,5Â4,3 mg/g-Cr, p<0,001), urinary MDA (1,77Â1,31 vs 1,27Â0,66 mmol/g-Cr, p=0,0372) and urinary MCP-1 (101Â79,8 vs 34,5Â14,9 mg/g-Cr, p=0,006) than healthy controls. Urinary MCP-1 was higher in multibacillary than in paucibacillary patients (122,1Â91,9 vs 72Â46,1 mg/g-Cr, p=0,023). There was a positive correlation between urinary MCP-1 and bacteriological index in skin smear (r=0,104; p=0,035), urinary MCP-1 and albumin excretion rate (r=0,171; p=0,006) and urinary MCP1 and urinary MDA (r=0,205; p=0,002). Conclusion: Leprosy patients with no clinical kidney disease have increased urinary MCP-1 and its levels are even higher according patients approximates to lepromatous polar form. Moreover, urinary MCP-1 was associated with urinary oxidative stress and urine albumin excretion, suggesting these patients are at increased risk of developing clinical kidney disease in the future.

The interaction between CD40 ligand (CD154) expressed on activated T cells and its receptor, CD40, has been shown to play a role in the onset and maintenance of autoimmune inflammation. Recent studies suggest that CD154+T cells also contribute to the regulation of atherogenesis due to their capacity to activate CD40+cells of the vasculature, including vascular smooth muscle cells (VSMC). The present study evaluated the signalling events initiated through CD40 ligation which culminate in VSMC chemokine production. CD40 ligation resulted in the phosphorylation/activation of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38, but not c-jun N-terminal kinase. Inhibition of both ERK1/2 and p38 activity abrogated CD40 stimulation of IL-8 and MCP-1 production. CD40-mediated induction of chemokines also showed dependence on the Src family kinase activity. The Src kinase inhibitor, PP2, was found to inhibit CD40-induced phosphorylation of ERK1/2 as well as activation of IκB kinase. An evaluation of Src kinases that may be important in CD40 signalling identified Lyn as a potential candidate. These data indicate that CD40 signalling in VSMC activates a Src family kinase-initiated pathway that results in the induction of MAPK activities required for successful induction of chemokine synthesis.

No description available.

No description available.

A hidroquinona (HQ) é um composto fenólico de origem natural ou antropogênica, encontrada em grandes concentrações no cigarro, além de ser produto da biotransformação do benzeno. Nosso grupo de pesquisa tem demonstrado que a exposição à HQ compromete a resposta inflamatória in vivo. Dando continuidade a estas investigações, este trabalho visou investigar os efeitos da exposição in vivo à HQ sobre funções do tecido traqueal e atividades de macrófagos alveolares. Para tanto, camundongos Swiss machos foram expostos à HQ 25ppm (1,5mg/60mL/1h; 5 dias) ou veículo (solução salina etanol 1:20) por via sistêmica (nebulização). Concentrações de mediadores inflamatórios (interleucina (IL) 1&#946;, IL-6, IL-10, IL-4, IL-12 fator de necrose tumoral-&#945; (TNF-&#945;) ou proteína quimiotáxica de monócitos (MCP-1); ensaio imunoenzimático (ELISA) e óxido nítrico (NO; reação de Griess) foram quantificados no lavado bronco-alveolar (LBA) em condições basais ou 3 horas após estímulo inflamatório (LPS in vivo; 100µL/mL; 10min) e no sobrenadante de macrófagos (M&#934;s) alveolares ou de cultura da traquéia obtidos dos animais e posteriormente estimulados in vitro (M&#934;s: 5µg/mL de LPS + 10ng/mL de IFN-&#947;; traquéia: 1µg/mL de LPS; 24h). Atividades fagocítica e fungicida (microscopia óptica) e a expressão de receptores envolvidos na fagocitose toll-like receptor (TLR, TLR-2, TLR4 e dectina-1; citometria de fluxo) foram determinadas após incubação in vitro de M&#934;s alveolares com o fungo Candida albicans e a expressão protéica de MyD88 foi realizada em M&#934;s alveolares (western blot). Quantificação do RNAm para MCP-1 (reação da transcriptase reversa em cadeia de polimerase, RT-PCR) foi realizada em tecido traqueal e células de linhagem monocítica humana THP-1 foram empregadas em ensaios de quimiotaxia in vitro (Câmara de Boyden) frente a diferentes concentrações de MCP-1. Reatividade do tecido traqueal foi quantificada frente à metacolina. Os resultados obtidos mostraram que a exposição in vivo à HQ reduziu a concentração de MCP-1 (54,98% vs. controle LPS) e IL-12 (51,45% vs. controle LPS) no LBA após inflamação; reduziu a secreção de MCP-1 por M&#934;s (basal: 87,96%; LPS+INF-&#947;: 61,20%) e tecido traqueal em cultura (79,77% vs. controle LPS). Neste último tecido, a diminuição foi dependente da menor expressão gênica. Concentrações de MCP-1 semelhantes à detectada no sobrenadante de cultura de traquéia de animais expostos à HQ induziram migração de células THP-1 menor (38,2%) que à provocada pela concentração de MCP-1 no sobrenadante da cultura traquéia de animais controles. Traquéias de animais expostos à HQ apresentaram hiperreatividade (193,48%), a qual foi revertida pela remoção do epitélio traqueal. Adicionalmente, cultura de M&#934;s obtidos de animais expostos à HQ apresentaram maior atividade fagocítica (porcentagem de fagocitose: 36,30%; índice de fagocitose: 83,97%) e fungicida (68,47%), que não foram dependentes de alterações nos receptores TLR2, TLR4 e dectina-1, mas podem ser decorrentes da menor expressão protéica de MyD88. Em conjunto, os dados obtidos apontam para alterações importantes resultantes da exposição in vivo à HQ sobre funções de M&#934;s alveolares e do tecido traqueal que, em conjunto, podem ser determinantes para a toxicidade observada nestes animais que culmina com prejuízo na defesa do organismo. / Hydroquinone (HQ) is a phenolic compound of natural or anthropogenic source, also found in high concentrations in cigarette, as well as benzene´s metabolite. Our research group has demonstrated that exposure to HQ impairs in vivo inflammatory response. Following these investigations, this work aimed to study the effects of in vivo exposure to HQ on tracheal tissue and alveolar macrophages (M&#934;s) activities. For this purpose, male Swiss mice were systemically (aerolised) exposed to 25ppm HQ (1.5 mg/60mL/1h; 5 days) or vehicle (saline ethanol solution, 1:20). Concentrations of inflammatory mediators (interleukin (IL) IL-1&#946;, IL- 6, IL-10, IL-4, IL-12 tumor necrosis factor-&#945; (TNF-&#945; ) or monocyte chemoattractant protein (MCP-1); (enzyme immune assay, ELISA)) and nitric oxide (NO; Griess reaction) were quantified in bronchoalveolar lavage (BAL) at baseline or 3 hours after inflammatory stimulus (in vivo LPS, 100&#181;L/mL; 10min); in the supernatant of cultured alveolar macrophages (M&#934;s) or trachea obtained from animals and subsequently in vitro stimulated (M&#934;s: 5&#181;g/mL of LPS plus 10ng/mL IFN-&#947;; trachea: 1&#181;g/mL LPS; 24 hours). Phagocytic and fungicidal activities (light microscopy) and expression of receptors involved in phagocytosis (toll-like receptor (TLR, TLR2, TLR4 and dectin-1, flow cytometry) were determined after in vitro incubation of alveolar M&#934;s with Candida albicans fungus and expression of MyD88 pathway was held in alveolar M&#934;s (western blot). Quantification of mRNA for MCP-1 (reaction of reverse transcriptase polymerase chain reaction, RT-PCR) was performed in tracheal tissue and cells human monocytic THP-1 were used in in vitro chemotaxis assays (Boyden chamber) using different concentrations of MCP-1. Tracheal reactivity was measured in response to methacholine. The results showed that in vivo HQ exposure reduced the concentration of MCP-1 (54.98% vs. control) and IL-12 (51.45% vs. control) in the BAL after inflammation; decreased secretion of MCP-1 by M&#934;s (basal: 87.96%, LPS+INF-&#947;: 61.20%) and in tracheal culture after LPS stimulation (79.77% vs. control). In the latter tissue, the MCP-1 protein content was dependent on impaired gene expression. Concentrations of MCP-1 similar to those detected in the supernatant of tracheal from HQ exposed rats induced smaller migration of THP-1 cells (38.2%) than that evoked by the MCP-1 concentration obtained in trachea supernatants collected from control animals. Tracheas from HQ exposed rats showed hyper reactivity (193.48%), which was reversed by removal of the tracheal epithelium. Additionally, culture of M&#934;s obtained from HQ exposed rats showed increased phagocytic (percentage of phagocytosis: 36.30%; phagocytosis index: 83.97%) and fungicide activity (68.47%), which were not dependent on changes in the receptors TLR2, TLR4 and dectin-1, but could be due to reduced MyD88 expression. Together, these data point out important alterations on M&#934;s and trachea after in vivo HQ exposure, which may be crucial for the toxicity observed in these animals that culminates with impaired host defense.