Ana Paula Moreira

Universidade Estadual Paulista (Unesp)

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Karen A. Cavassani

Samueli Institute

Cory M. Hogaboam

Cedars-Sinai Medical Center

João S. Silva

Faculdades Integradas Aparício Carvalho

Ana Lúcia Coelho

Cedars-Sinai Medical Center

Marcos A. Rossi

Società Italiana di Fisica

Steven L. Kunkel

University of Michigan–Ann Arbor

Ugur B. Ismailoglu

University of Michigan–Ann Arbor

Fabrine Sales Massafera Tristão

Universidade de São Paulo

Nicholas W. Lukacs

University of Michigan–Ann Arbor

Cristiane M. Milanezi

Universidade de São Paulo

Cooperative Institutions

University of Michigan–Ann Arbor

Universidade de São Paulo

Universidade de Ribeirão Preto

Michigan United

Clinics Hospital of Ribeirão Preto

Universidade Brasil

Michigan Medicine

Universidade do Extremo Sul Catarinense

Pulmonary and Critical Care Associates

Universidade Federal de Minas Gerais

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TRAIL-Dependent Resolution of Pulmonary Fibrosis

Mediators of Inflammation (2018)

David M. Habiel Ana Paula Moreira Ugur B. Ismailoglu Michael Dunleavy Karen A. Cavassani

Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) was key to the resolution of bleomycin-induced pulmonary fibrosis. Both in vivo and in vitro studies demonstrated that Gr-1+TRAIL+ bone marrow-derived myeloid cells blocked the activation of lung myofibroblasts. Although soluble TRAIL was increased in plasma from IPF patients, the presence of TRAIL+ myeloid cells was markedly reduced in IPF lung biopsies, and primary lung fibroblasts from this patient group expressed little of the TRAIL receptor-2 (DR5) when compared with appropriate normal samples. IL-13 was a potent inhibitor of DR5 expression in normal fibroblasts. Together, these results identified TRAIL+ myeloid cells as a critical mechanism in the resolution of pulmonary fibrosis, and strategies directed at promoting its function might have therapeutic potential in IPF.

Myofibroblast

10.1155/2018/7934362

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Citations (9)

Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis

PLoS ONE (2011)

Karen A. Cavassani Fabrine Sales Massafera Tristão Leandro Licursi de Oliveira Fernanda A. Rocha Jaqueline O. Vancim

The thermally dimorphic fungus Paracoccidioides brasiliensis (Pb) is the causative agent of paracoccidioidomycosis (PCM), one of the most frequent systemic mycosis that affects the rural population in Latin America. PCM is characterized by a chronic inflammatory granulomatous reaction, which is consequence of a Th1-mediated adaptive immune response. In the present study we investigated the mechanisms involved in the immunoregulation triggered after a prior contact with cell-free antigens (CFA) during a murine model of PCM. The results showed that the inoculation of CFA prior to the infection resulted in disorganized granulomatous lesions and increased fungal replication in the lungs, liver and spleen, that paralleled with the higher levels of IL-4 when compared with the control group. The role of IL-4 in facilitating the fungal growth was demonstrated in IL-4-deficient- and neutralizing anti-IL-4 mAb-treated mice. The injection of CFA did not affect the fungal growth in these mice, which, in fact, exhibited a significant diminished amount of fungus in the tissues and smaller granulomas. Considering that in vivo anti-IL-4-application started one week after the CFA-inoculum, it implicates that IL-4-CFA-induced is responsible by the mediation of the observed unresponsiveness. Further, the characterization of CFA indicated that a proteic fraction is required for triggering the immunosuppressive mechanisms, while glycosylation or glycosphingolipids moieties are not. Taken together, our data suggest that the prior contact with soluble Pb antigens leads to severe PCM in an IL-4 dependent manner.

Paracoccidioides

10.1371/journal.pone.0021423

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Citations (20)

Postural Education Programmes with School Children: A Scoping Review

Sustainability (2023)

Cristina Lima Araújo Ana Paula Moreira Graça Simões de Carvalho

Spinal deformities and back pain are growing problems in childhood and adolescence, due to unhealthy habits. This study undertook a scoping review to identify scientific studies with children and adolescents, focusing on the methodologies used, implementation of key factors and gaps, and results of postural education programmes to promote sustainable healthy habits. The methodological tool PRISMA-ScR was used. Five online databases were used to identify papers published since 2013. Eligibility criteria were defined, and the search strategies were drafted. A total of 86 publications were initially identified; after screening and applying eligibility criteria, 11 papers were included in this study for detailed analysis. The postural education programmes in these papers mainly focused on adolescents’ postures and postural learning acquisition, using different teaching methodologies; only one study was conducted with children between 5 and 6 years old enrolled in preschool. Follow-up studies revealed inconsistent results. However, developing and measuring the effectiveness of young children’s postural education programmes, to enhance experiences of movement variability and strategies for postural control in playful activities, is of great relevance for children’s healthy development, and can also have positive impacts on environmental and social sustainability by promoting healthy and conscious lifestyles.

Relevance

10.3390/su151310422

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Targeting ST2L Potentiates CpG-Mediated Therapeutic Effects in a Chronic Fungal Asthma Model

American Journal Of Pathology (2011)

Hemanth Ramaprakash Takehiko Shibata Karen E. Duffy Ugur B. Ismailoglu Rachel M. Bredernitz

TLR9

10.1016/j.ajpath.2011.03.032

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Macrophages in Allergic Asthma: Fine-Tuning Their Pro- and Anti-Inflammatory Actions for Disease Resolution

Journal of Interferon & Cytokine Research (2011)

Ana Paula Moreira Cory M. Hogaboam

Macrophages exert prominent effects in the defense of the respiratory tract from airborne pathogens. These cells are specialized to recognize, phagocytose, and destroy these infectious agents and then promote appropriate tissue repair after successful pathogen clearance. For reasons that are not presently clear, macrophages appear to be inappropriately activated during asthma responses. Evidence stems from the appearance of either classically (or M1) and alternatively activated (or M2) cells in the alveolar compartment of asthmatic lung. Macrophages localized in the interstitial area of the lung appear to be less prone to polarization toward either the M1 or M2 phenotype as these cells predominately express interleukin-10 and exhibit immunoregulatory properties. Effective treatment of clinical asthma, regardless of severity, might depend on restoring an appropriate balance between M1, M2, and immunoregulatory macrophages in the lung.

Respiratory tract

Macrophage polarization

10.1089/jir.2011.0027

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Citations (135)

Role of Growth Arrest–Specific Gene 6 in the Development of Fungal Allergic Airway Disease in Mice

American Journal of Respiratory Cell and Molecular Biology (2014)

Takehiko Shibata Ugur B. Ismailoglu Nicolai A. Kittan Ana Paula Moreira Ana Lúcia Coelho

Growth arrest-specific gene (Gas)6 is a secreted vitamin K-dependent protein with pleiotropic effects via activation of receptor tyrosine kinase Tyro3, Axl, and Mertk receptors, but little is known about its role in allergic airway disease. We investigated the role of Gas6 in the development of fungal allergic airway disease in mice. The immune response was evaluated in Gas6-deficient (Gas6-/-) and wild-type (WT) mice and in recombinant Gas6-treated WT mice during Aspergillus fumigatus-induced allergic airway disease. Gas6 plasma levels were significantly elevated in adult clinical asthma of all severities compared with subjects without asthma. In a murine model of fungal allergic airway disease, increased protein expression of Axl and Mertk were observed in the lung. Airway hyperresponsiveness (AHR), whole lung Th2 cytokine levels, goblet cell metaplasia, and peribronchial fibrosis were ameliorated in Gas6-/- mice compared with WT mice with fungal allergic airway disease. Intranasal Gas6 administration into WT mice had a divergent effect on airway inflammation and AHR. Specifically, a total dose of 2 μg of exogenous Gas6 (i.e., low dose) significantly increased whole lung Th2 cytokine levels and subsequent AHR, whereas a total dose of 7 μg of exogenous Gas6 (i.e., high dose) significantly suppressed Th1 and Th2 cytokines and AHR compared with appropriate control groups. Mechanistically, Gas6 promoted Th2 activation via its highest affinity receptor Axl expressed by myeloid DCs. Intranasal administration of Gas6 consistently exacerbated airway remodeling compared with control WT groups. These results demonstrate that Gas6 enhances several features of fungal allergic airway disease.

10.1165/rcmb.2014-0049oc

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Citations (19)

Wheelchair handball classification system: purpose and validation evidence-based

International Physical Medicine & Rehabilitation Journal (2024)

Nuno Januário José Antunes Vilela de Carvalho J Sara Fernandes Daniela Ferreira

The aim of the present work is to propose and validate an evidence-based Wheelchair Handball Classification System, that allows its widespread use and the standardization of the classification system in different Wheelchair Handball competitions. The study involved 98 Wheelchair Handball athletes of both sex (87 males, 11 females), aged between 14 and 76 years old (M=40.32; SD= 11.73) with physical impairments. All wheelchair handball players that had participated in the last 3 national championships were invited to participate. We applied the assessment protocol to the participants and athletes’ classification process had three phases: Medical and Physiological functional assessment; Technical assessment (evaluation of specific movements with wheelchair manipulation and Handball skills) and observation in a game situation (with videorecorder). We used a Classification Points Form to permit the assessment of muscle strength and range of movement of upper limbs, trunk, lower limbs, wheelchair manipulation and Handball skills. The manipulation of wheelchair was measured considering the symmetrical movement, acceleration, braking and change direction, using the Sprint 20m – speed test and a Slalom test. The handball skills were assessed, using dribbling, reception, catching the ball from the floor, shoulder and shopped pass and 9m to the goal shot. Data Analysis was done using descriptive statistics and an Ordinal Linear Regression. The dependent variable was the classification class and we considered five independent variables (mean of upper limbs, trunk, lower limbs, wheelchair manipulation and Handball skills). Data Analysis was done using IBM SPSS Statistics. The results showed that the proposed model presents a high degree of adjustment and permitted identify determinant variables of performance in that sport and indicates key tasks to optimize classification process. There was consistency in the specific parameters to assign a class to the athlete, according to their functional capacity, associated with the specific neuromotor alterations of each clinical condition.

Sprint

10.15406/ipmrj.2024.09.00366

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Citations (1)

CCR5-Dependent Regulatory T Cell Migration Mediates Fungal Survival and Severe Immunosuppression

The Journal of Immunology (2008)

Ana Paula Moreira Karen A. Cavassani Fabrine Sales Massafera Tristão Ana Paula Campanelli Roberto Martínez

Abstract Paracoccidioidomycosis, a debilitating pulmonary mycosis, is caused by the dimorphic fungus Paracoccidioides brasiliensis. The infection results in the formation of granulomas containing viable yeast cells that are the fungal sources for disease reactivation. Because CD4+CD25+ regulatory T cells (Tregs) are in the lesions of patients with paracoccidioidomycosis, the migration of Treg cells is dependent on the axis chemokine-chemokine receptors, and CCR5 ligands are produced in P. brasiliensis-induced lesions, we investigated the role of CCR5 in the control of the infection. The results showed that CCR5−/− mice are more efficient in controlling fungal growth and dissemination and exhibited smaller granulomas than wild-type (WT) mice. In the absence of CCR5, the percentage of CD4+CD25+ T cells expressing Foxp3, glucocorticoid-induced TNFR (GITR), CD103, CD45low, and CTLA-4 in the granulomas was significantly decreased. Interestingly, P. brasiliensis infection resulted in an absence of T cell proliferation in response to Con A in WT but not CCR5−/− mice that was abrogated by anti-CTLA-4 mAb and anti-GITR mAb. Moreover, the adoptive transfer of CD4+CD25+ but not CD4+CD25− T cells from infected WT to infected CCR5−/− mice resulted in a significant increase in fungal load. Overall, CCR5 is a key receptor for the migration of Treg cells to the site of P. brasiliensis infection, leading to down-modulation of effector immune response and the long-term presence of the fungus in the granulomas. Thus, a tight control of Treg cell migration to the granulomatous lesions could be an important mechanism for avoiding exacerbation and reactivation of the disease.

Adoptive Cell Transfer

10.4049/jimmunol.180.5.3049

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Citations (114)

Serum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages

PLoS ONE (2010)

Lynne A. Murray Rogério Silva Rosada Ana Paula Moreira Amrita Joshi Michael S. Kramer

Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcgamma receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which may extend to many fibrotic indications caused by over-exuberant pro-fibrotic macrophage responses.

Alveolar macrophage

10.1371/journal.pone.0009683

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Citations (189)

Desenvolvimento invisível da humanidade cotidiana: Psicologia, Biologia e Cultura

Obutchénie Revista de Didática e Psicologia Pedagógica (2023)

Ana Paula Moreira Guilherme Brockington

Este trabalho organiza-se como um estudo teórico, cujo objetivo é debater as implicações da cisão entre a ciências naturais e as ciências humanas para o campo de estudos da Psicologia do Desenvolvimento. Reitera-se que esta cisão irrefletida tem sido perniciosa tanto para a construção quanto para a interpretação de resultados de pesquisas, especialmente, no âmbito daqueles estudos dedicados ao desenvolvimento das funções psicológicas superiores. Pretendemos resgatar o lastro da Psicologia Soviética bem como alguns interlocutores da neurociência contemporânea para acentuar que a necessidade de superação desta ruptura já havia sido anunciada e, de muitas maneiras, continua sendo incentivada. Enfatizamos a arena da linguagem como marco orientador desta análise na medida em que aglutina dimensões da síntese entre Biologia e Cultura. Os desdobramentos desta compreensão contribuem, especialmente, com discussões no campo da Psicologia e da Educação.

10.14393/obv7n1.a2023-57834

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