Influenza A virus (IAV) is a major cause of morbidity and mortality worldwide. Surfactant proteins A and D (SP-A and SP-D) are important lung innate immune proteins and have been shown in vitro and in mice to both neutralize and enhance the clearance of various IAV strains. In this study we hypothesized that SP-A and SP-D levels will be lower in human bronchoalveolar lavage (BAL) fluids from patients who have tested positive for influenza, as well as bacterial or fungal pathogens compared to controls. We have found that patients who have detectable IAV, bacteria or fungus have lower levels of SP-A and SP-D as detected by western blot analysis and enzyme-linked immunosorbent assay (ELISA) when compared to controls. Also, we found minor differences in the oligomerization and no differences in the glycosylation of SP-A and SP-D among BALs that detected the proteins on a Western blot.

Influenza A virus (IAV) is a major cause of morbidity and mortality worldwide. Surfactant proteins A and D (SP-A and SP-D) are important lung innate immune proteins and have been shown in vitro and in mice to both neutralize and enhance the clearance of various IAV strains. In this study we hypothesized that SP-A and SP-D levels will be lower in human bronchoalveolar lavage (BAL) fluids from patients who have tested positive for influenza, as well as bacterial or fungal pathogens compared to controls. We have found that patients who have detectable IAV, bacteria or fungus have lower levels of SP-A and SP-D as detected by western blot analysis and enzyme-linked immunosorbent assay (ELISA) when compared to controls. Also, we found minor differences in the oligomerization and no differences in the glycosylation of SP-A and SP-D among BALs that detected the proteins on a Western blot.

La DM 2 és una malaltia multifactorial i multigènica. Aquest fet condueix a l'estudi de molts gens i proteïnes susceptibles d'estar implicades amb la DM 2. Algunes d'aquestes proteïnes i gens estan associats a un estat lleu d'inflamació crònica, la qual pot desencadenar la síndrome metabòlica (SRI) i DM 2. Moltes d'aquestes proteïnes poden usar-se com a possibles marcadors de malaltia cardiovascular, resistència a la insulina i futura DM 2. Aquest treball presenta quatre proteïnes i la seva relació amb la SRI i la DM 2. L'SP-D i l'SP-A s'estudien per la relació que hi ha entre la disminució de la funció pulmonar i la resistència a la insulina i pel fet de ser moduladores de la inflamació. Les α-defensines s'estudien perquè també són moduladores de la inflamació i per una possible relació amb l'arteriosclerosi i el colesterol LDL. La visfatina s'estudia per la possible associació amb la insulinosecreció. / Type 2 diabetes (T2DM) is a multifactorial and multigenic disease. This fact drives in the study of many genes and proteins susceptible of being implied with T2DM. Some of these proteins and gens are associated inlow-grade chronic inflammation, which can unchain metabolic syndrome (SRI) and T2DM. Many of these proteins can be used as possible markers of cardiovascular disease, insulin resistance and T2DM. This work presents four proteins and their association with SRI and T2DM. SP-D and the SP-A have been studied since there are a association among the decrease of the pulmonary function and insulin resistance. These proteins modulates inflammation too.α-defensins are studied also because they are modulate inflammation; and because there are a possible association among arteriosclerosis, cholesterol LDL and α-defensins. The visfatina is studied by the possible association with insulin secretion.

No description available.

L’étude des marqueurs biologiques dans la broncho-pneumopathie chronique obstructive (BPCO) et l'asthme, deux maladies respiratoires chroniques affectant des millions de personnes dans le monde, pourrait améliorer leur diagnostic, leur traitement et leur prévention.Cette thèse comprend deux parties. La première visait à évaluer l'association entre un marqueur spécifique des poumons, la protéine surfactant D (SP-D) sérique, et la BPCO, et à trouver un seuil de SP-D capable de discriminer les patients BPCO des témoins. Elle a été réalisée dans le cadre d’une étude cas-témoin au Liban incluant des patients BPCO (n=90), des asthmatiques (n=124) et des témoins (n=180). La deuxième partie visait à évaluer les associations chez les adultes des marqueurs de l’inflammation systémique (protéine C-réactive ultra-sensible, hs-CRP (n=252), et des cytokines (n=283)) et des marqueurs de dommages dus au stress oxydant (8-isoprostanes 8-IsoPs (n=258) du condensat de l’air exhalé) avec les phénotypes de l’asthme.Elle a été réalisée dans le cadre de l'étude épidémiologique longitudinale Française des facteurs génétiques et environnementaux de l'asthme (EGEA).Les résultats ont montré que les niveaux de SP-D sériques étaient associés positivement avec la BPCO et des seuils des niveaux de SP-D chez ces patients ont été identifiés avec d'excellentes valeurs discriminantes. Dans EGEA, aucune association n'a été trouvée entre les niveaux de hs-CRP sériques et le contrôle de l’asthme. Des profils de cytokines sériques (identifiés par analyse en composante principale) avec des niveaux élevés d’interleukine(IL)-1Ra et d’IL-10 ont été associés avec moins de crises d'asthme et un risque plus faible d'un mauvais contrôle de l'asthme sept ans plus tard. Les résultats des analyses préliminaires sur les associations entre les niveaux de 8-IsoPs et les phénotypes de l'asthme sont également présentés.Globalement, ces résultats ont montré l'utilité d'étudier les marqueurs biologiques en lien avec la BPCO et l'asthme. / Studying the biological markers in chronic obstructive pulmonary disease (COPD) and asthma, two chronic respiratory diseases affecting millions of individuals around the world, could improve their diagnosis, their treatment and their prevention.This thesis includes two parts. The first aimed to assess the association between a lung-specific biomarker, serum Surfactant Protein D (SP-D), and COPD, and to find cut-off points able to discriminate COPD patients from controls using SP-D levels. It was performed in a case-control study in Lebanon including COPD (n=90) and asthma patients (n=124) and controls (n=180). The second part aimed to assess the cross-sectional and longitudinal associations in adults for systemic inflammatory biomarkers (high sensitivity C reactive protein hs-CRP (n=252) and cytokines (n=283) as well as biomarkers of damage due to oxidative stress (8-Isoprostanes 8-IsoPs (n=258) from the exhaled breath condensate) and asthma outcomes.It was performed in the French longitudinal epidemiological study on the genetics and environmental factors of asthma (EGEA).Results showed that serum SP-D levels were positively associated with COPD and thresholds for SP-D levels in these patients were identified with excellent discriminant values. In EGEA, no association was found between serum hs-CRP levels and asthma control. Serum cytokine profiles (identified by principal component analysis) with high levels of interleukin (IL)-1Ra and IL-10 were associated with less asthma attacks and lower risk of poor asthma control in adults seven years later. The results of the preliminary analyses on the associations between the levels of 8-IsoPs and asthma outcomes are also presented.Overall, these results have shown the usefulness of studying the biological markers related to COPD and asthma.

No description available.

The innate immune protein surfactant protein (SP-) D is a carbohydrate binding protein that was originally isolated from mucosal lung tissues. Recently, studies show that SP-D binds to antibodies, including immunoglobulin M (IgM), which interacts with late apoptotic cells. Here we focus on the interaction between SP-D and IgM as they pertain to late apoptotic cell clearance. We hypothesized that the three-way interaction between IgM, SP-D and late apoptotic cells is functionally applicable to clearing late apoptotic cells from the lungs, thereby reducing lung inflammation. We show that SP-D binds to IgM and that IgM binds to the late apoptotic subclass of dying cells. We demonstrate that IgM and SP-D can both bind to late apoptotic cells in mutually distinct regions while also displaying some regional overlap. We show evidence that during LPS-induced lung inflammation both IgM and SP-D levels are elevated and this corresponds to an augmentation of apoptotic cell clearance. We illustrate that the protein interaction of IgM and SP-D is functionally relevant to apoptotic cell clearance in the lungs by showing that late apoptotic cells coated in IgM and/or SP-D are cleared more efficiently than control cells, by alveolar macrophages in vivo. Our ex vivo studies further show that these cells internalize apoptotic cells by engulfing very small particles released from the dying cells. We then showed that IgM preferentially directs the engulfment of small particles (~1 μm) by macrophages, in an apparent size-specific antibody-dependent particle clearance function. Our data reveals a novel relationship amongst IgM, SP-D, apoptotic cells, and alveolar macrophages that contributes to our understanding of apoptotic cell clearance, which may be used in the future to generate strategies addressing apoptotic cell accumulation or clearance deficiency in disease.

The innate immune protein surfactant protein (SP-) D is a carbohydrate binding protein that was originally isolated from mucosal lung tissues. Recently, studies show that SP-D binds to antibodies, including immunoglobulin M (IgM), which interacts with late apoptotic cells. Here we focus on the interaction between SP-D and IgM as they pertain to late apoptotic cell clearance. We hypothesized that the three-way interaction between IgM, SP-D and late apoptotic cells is functionally applicable to clearing late apoptotic cells from the lungs, thereby reducing lung inflammation. We show that SP-D binds to IgM and that IgM binds to the late apoptotic subclass of dying cells. We demonstrate that IgM and SP-D can both bind to late apoptotic cells in mutually distinct regions while also displaying some regional overlap. We show evidence that during LPS-induced lung inflammation both IgM and SP-D levels are elevated and this corresponds to an augmentation of apoptotic cell clearance. We illustrate that the protein interaction of IgM and SP-D is functionally relevant to apoptotic cell clearance in the lungs by showing that late apoptotic cells coated in IgM and/or SP-D are cleared more efficiently than control cells, by alveolar macrophages in vivo. Our ex vivo studies further show that these cells internalize apoptotic cells by engulfing very small particles released from the dying cells. We then showed that IgM preferentially directs the engulfment of small particles (~1 μm) by macrophages, in an apparent size-specific antibody-dependent particle clearance function. Our data reveals a novel relationship amongst IgM, SP-D, apoptotic cells, and alveolar macrophages that contributes to our understanding of apoptotic cell clearance, which may be used in the future to generate strategies addressing apoptotic cell accumulation or clearance deficiency in disease.

L'étude des propriétés électroniques et magnétiques des structures à un puits quantique CdMnTe à modulation de dopage de type-n nous a permis d'explorer l'interaction d ‘échange sp-d entre les électrons 2D délocalisés et les moments magnétiques localisés des ions Mn2+. Cette interaction d'échange sépare les états de spin électronique induisant un splitting Zeeman géant lequel modifie profondément les propriétés électroniques et optiques du semi-conducteur. A faible champ magnétique, l'interaction sp-d peut être décrite par une approximation de champ moyen. Néanmoins, à fort champ magnétique nous observons qu'une énergie effective Zeeman nulle n'entraîne pas la disparition complète du gap de spin. En effet, des expériences de transport et de spectroscopie Raman montrent une répulsion entre les niveaux de spin up et down. Nos résultats peuvent être expliqués dans le cadre d'un modèle basé sur l'anti-croisement des niveaux de Landau résolus en spin. Les propriétés magnétiques du sous-système d'ions Mn2+ sont fortement influencées par la présence des porteurs. Le ‘Knight shift' observé pour la position du spectre RPE peut être décrit par l'approximation de champ moyen pour de faibles champs. Cependant, cette approximation ne permet pas de décrire la valeur importante du ‘Knight shift' à fort champ au voisinage de EMnZ=EeZ. Pour interpréter nos résultats expérimentaux de spectroscopie Raman et de RPE nous proposons un modèle basé sur l'interaction résonante entre les excitations de spin pour les électrons et pour les ions Mn2+. Finalement, une étude de l'évolution de la réponse optique des puits quantiques CdMnTe en fonction de la concentration d'électrons montre une persistance des effets excitoniques lorsque l'énergie de Fermi est comparable à l'énergie de liaison excitonique. Suite à nos recherches, l'homogénéité de nos systèmes est remise en cause.

No description available.