Expression of RANTES, eotaxin-2, ICAM-1, LFA-1 and CCR-3 in chronic rhinosinusitis patients with nasal polyposis / Expressão de RANTES, eotaxina-2, ICAM-1, LFA-1 e CCR-3 em pacientes com rinossinusite crônica associada à polipose nasossinusal

PURPOSE: To compare gene expression of the chemokines RANTES and eotaxin-2, its receptor, CCR-3, adhesion molecule ICAM-1 and its receptor LFA-1 in eosinophilic polyps and in control normal nasal mucosa. METHODS: Gene expression was quantified by Real Time PCR in polyps (n=35) and in healthy nasal mucosa (n=15). RESULTS: Eosinophilic polyps showed a higher expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa. CONCLUSION: Eosinophilic polyps present greater expression of eotaxin-2 and RANTES, but not of CCR-3, ICAM-1 or LFA-1 compared to control nasal mucosa.

OBJETIVO: Comparar a expressão gênica das quimiocinas RANTES e eotaxina-2, do seu receptor CCR-3, da molécula de adesão ICAM-1 e do seu receptor LFA-1 entre pólipos nasais eosinofílicos (PE) (n=35) e mucosa nasal controle (n=15). MÉTODOS: Quantificou-se a expressão gênica dos mediadores citados pela técnica de PCR em tempo real em PEs e em mucosas de concha média de pacientes sem doenças nasais ou alteração endoscópica. RESULTADOS: Pólipos eosinofílicos apresentam maior expressão de eotaxina-2 e RANTES, mas não de CCR-3, ICAM-1 e LFA-1, quando comparados as mucosas nasais controles. CONCLUSÃO: Pólipos eosinofícios apresentaram maior expressão de eotaxin-2 and RANTES, mas não de CCR-3, ICAM-1 ou LFA-1,comparada à mucosa nasal controle.

Non-inflammatory destructive periodontal disease: a clinical, microbiological, immunological and genetic investigation

Periodontitis comprises a group of multifactorial diseases in which periodontopathogens accumulate in dental plaque and trigger host chronic inflammatory and immune responses against periodontal structures, which are determinant to the disease outcome. Although unusual cases of non-inflammatory destructive periodontal disease (NIDPD) are described, their pathogenesis remains unknown. A unique NIDPD case was investigated by clinical, microbiological, immunological and genetic tools. The patient, a non-smoking dental surgeon with excessive oral hygiene practice, presented a generalized bone resorption and tooth mobility, but not gingival inflammation or occlusion problems. No hematological, immunological or endocrine alterations were found. No periodontopathogens (A. actinomycetemcomitans, P. gingivalis, F. nucleatum and T. denticola) or viruses (HCMV, EBV-1 and HSV-1) were detected, along with levels of IL-1β and TNF-a in GCF compatible with healthy tissues. Conversely ALP, ACP and RANKL GCF levels were similar to diseased periodontal sites. Genetic investigation demonstrated that the patient carried some SNPs, as well HLA-DR4 (*0404) and HLA-B27 alleles, considered risk factors for bone loss. Then, a less vigorous and diminished frequency of toothbrushing was recommended to the patient, resulting in the arrest of alveolar bone loss, associated with the return of ALP, ACP and RANKL in GCF to normality levels. In conclusion, the unusual case presented here is compatible with the previous description of NIDPD, and the results that a possible combination of excessive force and frequency of mechanical stimulation with a potentially bone loss prone genotype could result in the alveolar bone loss seen in NIDPD.

In vitro initial immune response against Leishmania amazonensis infection is characterized by an increased production of IL-10 and IL-13

The initial encounter of Leishmania with its host's immune system is important in the outcome of infection. Previous studies have shown that PBMCs from healthy volunteers (HV) exposed to Leishmania differ in IFN-γ production. We have expanded such observations evaluating the profile and kinetics of cytokines (IFN-γ, IL-12p70, IL-10, IL-13), chemokines (CCL5, CCL3, CCL4, CXCL10), and chemokine receptors (CCR1,CCR5, CXCR3, CCR4) in vitro L. amazonensis-stimulated of HV's PBMCs. HVs were divided in groups of high (HR) or low (LR) IFN-γ responders. In both groups, HR and LR, after L. amazonensis infection there was a predominance of IL-10 and IL-13 over IFN-γ production, while IL-12 was produced in similar amount. Regarding chemokines, a more striking difference was observed for CCL3 expression that was lower at 12 hours and 48 hours post infection in LR than in HR. Interestingly, a downregulation of CCR5 and a greater expression of CCR4 were found in low IFN-γ responders. These data suggest that early after L. amazonensis infection there is a cytokine milieu dominated by IL-13 and IL-10, and despite of this environment, IFN-γ is produced, supporting the complexity of the response. It is noteworthy that the pattern of immune response is mounted in first hours after Leishmania stimulation, with the definition of the differentiation of Th1 versus Th2 cells. It remains to be determined if such an in vitro difference has an in vivo counterpart in terms of susceptibility to infection.

Tumor-infiltrating CD4+ T lymphocytes in early breast cancer reflect lymph node involvement

INTRODUÇÃO: O papel do sistema imunológico na patogênese e progressão do câncer de mama ainda é controverso, e isto nos estimulou a verificar a associação do imunofenótipo dos linfócitos tumor infiltrantes do câncer de mama inicial com a disseminação de células tumorais para os linfonodos axilares. MÉTODOS: Amostras tumorais de 23 pacientes com câncer de mama inicial do Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto (USP) foram obtidas no momento da biópsia e depois submetidas ao método de digestão enzimática para a extração dos linfócitos tumor infiltrantes. Os linfócitos extraídos foram analisados por citometria de fluxo com anticorpos monoclonais nas seguintes combinações: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, e CD16/56 PerCP, específicos para imunofenotipagem de linfócitos T e B, linfócitos T helper, linfócitos citotóxicos, e células Natural Killer. Os valores médios destas subpopulações leucocitárias foram comparados entre grupos de pacientes com ou sem metástases linfonodais. RESULTADOS: O valor médio do infiltrado por linfócitos T foi 24,72±17,37%, para o infiltrado por linfócitos B foi 4,22±6,27%, e para o infiltrado por células Natural Killer foi 4,41±5,22%, e para o infiltrado por linfócitos T CD4+ e CD8+ foram, respectivamente, 12,43±10,12% e 11,30±15,09%. Os valores médios do infiltrado por células T e T CD4+ foram maiores no grupo de pacientes com metástase axilar, enquanto nas outras subpopulações nada foi encontrado.CONCLUSÃO: A associação dos linfócitos T CD4+ tumor infiltrantes com metástases linfonodais sugere um papel destas células na disseminação das células neoplásicas aos linfonodos dos pacientes com câncer de mama inicial.