MARISA DOLHNIKOFF
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
5 resultados
Resultados de Busca
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- Immunopathological aspects of schistosomiasis-associated pulmonary arterial hypertension(2014) MAUAD, Thais; POZZAN, Geanette; LANCAS, Tatiana; OVERBEEK, Maria J.; SOUZA, Rogerio; JARDIM, Carlos; DOLHNIKOFF, Marisa; MELLO, George; PIRES-NETO, Ruy Camargo; BERNARDI, Fabiola del Carlo; GRUNBERG, KatrienObjectives: Pulmonary hypertension is a lethal complication of chronic hepatosplenic schistosomiasis. Little is known of the underlying (immuno-)histopathological characteristics of lung vasculopathy. Methods: We characterized vasculopathy and inflammation in lung tissue of 10 patients with Schistosomiasis-associated PH (SCH-PH) in comparison to 22 idiopathic pulmonary arterial hypertension (IPAH) patients and 10 normal controls. SCH-PH cases were younger than controls. Results: Plexiform lesions and/or angiomatoid lesions were found in 10/10 SCH-PH, and 19/22 IPAH patients (chi(2) p = 0.22). Lung granulomas with Schistosoma eggs were found in 2/10 of SCH-PH cases. PAH cases had increased peri-arterial density of CD3+ T cells, chymase+ and tryptase+ mast cells when compared to controls (p <= 0.047). SCH-PH showed increased density of CD4+ cells when compared to controls (p = 0.025), paralleled by an increased density of dendritic CD83+ cells when compared to both controls and IPAH patients (p <= 0.022). Conclusion: Both SCH-PH and IPAH feature plexogenic arteriopathy and increased periarterial T cell and mast cell density. SCH-PH and IPAH differ only with respect to the density of dendritic CD83+ cells. These findings imply ongoing antigenic stimulation in SCH-PH, yet a pattern of pulmonary vasculopathy similar to IPAH, suggestive of a final common pathway in their pathogenesis of PAH.
- Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma(2012) FERREIRA, D. S.; ANNONI, R.; SILVA, L. F. F.; BUTTIGNOL, M.; SANTOS, A. B. G.; MEDEIROS, M. C. R.; ANDRADE, L. N. S.; YICK, C. Y.; STERK, P. J.; SAMPAIO, J. L. M.; DOLHNIKOFF, M.; WENZEL, S. E.; MAUAD, T.Background Airway inflammation in asthma involves innate immune responses. Toll-like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics both large and small airways has not been investigated. Objective To analyse the expression of TLR2, TLR3, TLR4 and TSLP in large and small airways of asthmatics and compare their expression in smoking and non-smoking asthmatics; to investigate whether TLR expression is associated with eosinophilic or neutrophilic airway inflammation and with Mycoplasma pneumoniae and Chlamydophila pneumoniae infection. Methods Using immunohistochemistry and image analysis, we investigated TLR2, TLR3, TLR4 and TSLP expression in large and small airways of 24 victims of fatal asthma, FA, (13 non-smokers, 11 smokers) and nine deceased control subjects (DCtrl). TLRs were also measured in 18 mild asthmatics (MA) and 12 healthy controls (HCtrl). M. pneumoniae and C. pneumoniae in autopsy lung tissue were analysed using real-time polymerase chain reaction. Airway eosinophils and neutrophils were measured in all subjects. Results Fatal asthma patients had higher TLR2 in the epithelial and outer layers of large and small airways compared with DCtrls. Smoking asthmatics had lower TLR2 levels in the inner and outer layers of the small airways than non-smoking asthmatics. TSLP was increased in the epithelial and outer layers of the large airways of FA. FA patients had greater TLR3 expression in the outer layer of large airways and greater TLR4 expression in the outer layer of small airways. Eosinophilic airway inflammation was associated with TLR expression in the epithelium of FA. No bacterial DNA was detected in FA or DCtrls. MA and HCtrls had only a small difference in TLR3 expression. Conclusions and Clinical Relevance Increased expression of TLR 2, 3 and 4 and TSLP in fatal asthma may contribute to the acute inflammation surrounding asthma deaths.
- Extracellular matrix composition in COPD(2012) ANNONI, Raquel; LANCAS, Tatiana; TANIGAWA, Ryan Yukimatsu; MATSUSHITA, Marcus de Medeiros; FERNEZLIAN, Sandra de Morais; BRUNO, Andreina; SILVA, Luiz Fernando Ferraz da; ROUGHLEY, Peter J.; BATTAGLIA, Salvatore; DOLHNIKOFF, Marisa; HIEMSTRA, Pieter S.; STERK, Peter J.; RABE, Klaus F.; MAUAD, ThaisExtracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.
conferenceObject Granzyme A Expression In Fatal Asthma(2013) SILVA, L. F.; SANTOS, F. E.; ANNONI, R.; NUSSBAUMER-OCHSNER, Y.; DOLHNIKOFF, M.; RABE, K. F.; MAUAD, T.; HIEMSTRA, P.- Versican and collagen-III expression in bronchial and pulmonary muscular arteries in COPD patients(2015) ANNONI, Raquel; COUCEIRO, Ligia; BARBOSA, Silvio; LANCAS, Tatiana; BATTAGLIA, Salvatore; DOLHNIKOFF, Marisa; HIEMSTRA, Pieter; STERK, Peter; RABE, Klaus; MAUAD, Thais