RESUMO
Lack of sleep greatly affects our immune system. The present study investigates the acute effects of total sleep deprivation on blood neutrophils, the most abundant immune cell in our circulation and the first cell type recruited to sites of infection. Thus, the population diversity and function of circulating neutrophils were compared in healthy young men following one night of total sleep deprivation (TSD) or after 8h regular sleep. We found that neutrophil counts were elevated after nocturnal wakefulness (2.0 ± 0.2 × 10(9)/l vs. 2.6 ± 0.2 × 10(9)/l, sleep vs. TSD, respectively) and the population contained more immature CD16(dim)/CD62L(bright) cells (0.11 ± 0.040 × 10(9)/l [5.5 ± 1.1%] vs. 0.26 ± 0.020 × 10(9)/l [9.9 ± 1.4%]). As the rise in numbers of circulating mature CD16(bright)/CD62L(bright) neutrophils was less pronounced, the fraction of this subpopulation showed a significant decrease (1.8 ± 0.15 × 10(9)/l [88 ± 1.8%] vs. 2.1 ± 0.12 × 10(9)/l [82 ± 2.8%]). The surface expression of receptors regulating mobilization of neutrophils from bone marrow was decreased (CXCR4 and CD49d on immature neutrophils; CXCR2 on mature neutrophils). The receptor CXCR2 is also involved in the production of reactive oxygen species (ROS), and in line with this, total neutrophils produced less ROS. In addition, following sleep loss, circulating neutrophils exhibited enhanced surface levels of CD11b, which indicates enhanced granular fusion and concomitant protein translocation to the membrane. Our findings demonstrate that sleep loss exerts significant effects on population diversity and function of circulating neutrophils in healthy men. To which extent these changes could explain as to why people with poor sleep patterns are more susceptible to infections warrants further investigation.
Assuntos
Neutrófilos/imunologia , Privação do Sono/imunologia , Doença Aguda , Antígeno CD11b/biossíntese , Antígeno CD11b/genética , Núcleo Celular/ultraestrutura , Quimiotaxia de Leucócito , Proteínas Ligadas por GPI/análise , Voluntários Saudáveis , Humanos , Selectina L/análise , Contagem de Leucócitos , Masculino , Neutrófilos/química , Neutrófilos/classificação , Neutrófilos/metabolismo , Polissonografia , Espécies Reativas de Oxigênio/metabolismo , Receptores CXCR4/biossíntese , Receptores CXCR4/genética , Receptores de IgG/análise , Receptores de Interleucina-8B/biossíntese , Receptores de Interleucina-8B/genética , Explosão Respiratória , Adulto JovemRESUMO
In vivo leukocyte recruitment is not fully understood and may result from interactions of chemokines with glycosaminoglycans/GAGs. We previously showed that chlorite-oxidized oxyamylose/COAM binds the neutrophil chemokine GCP-2/CXCL6. Here, mouse chemokine binding by COAM was studied systematically and binding affinities of chemokines to COAM versus GAGs were compared. COAM and heparan sulphate bound the mouse CXC chemokines KC/CXCL1, MIP-2/CXCL2, IP-10/CXCL10 and I-TAC/CXCL11 and the CC chemokine RANTES/CCL5 with affinities in the nanomolar range, whereas no binding interactions were observed for mouse MCP-1/CCL2, MIP-1α/CCL3 and MIP-1ß/CCL4. The affinities of COAM-interacting chemokines were similar to or higher than those observed for heparan sulphate. Although COAM did not display chemotactic activity by itself, its co-administration with mouse GCP-2/CXCL6 and MIP-2/CXCL2 or its binding of endogenous chemokines resulted in fast and cooperative peritoneal neutrophil recruitment and in extravasation into the cremaster muscle in vivo. These local GAG mimetic features by COAM within tissues superseded systemic effects and were sufficient and applicable to reduce LPS-induced liver-specific neutrophil recruitment and activation. COAM mimics glycosaminoglycans and is a nontoxic probe for the study of leukocyte recruitment and inflammation in vivo.
Assuntos
Quimiocinas/metabolismo , Glicosaminoglicanos/metabolismo , Inflamação/patologia , Infiltração de Neutrófilos , Sequência de Aminoácidos , Amilose/análogos & derivados , Amilose/metabolismo , Amilose/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Quimiocinas/química , Quimiocinas/farmacologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Feminino , Heparitina Sulfato/metabolismo , Inflamação/metabolismo , Injeções Intraperitoneais , Ponto Isoelétrico , Cinética , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Músculos/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Cavidade Peritoneal/citologia , Ressonância de Plasmônio de SuperfícieRESUMO
Sex differences in obesity-induced complications such as type 2 diabetes have been reported. The aim of the study was to pinpoint the mechanisms resulting in different outcome of female and male mice on a high-fat diet (HFD). Mice fed control or HFD were monitored for weight, blood glucose, and insulin for 14 weeks. Circulating chemokines, islet endocrine function and blood flow, as well as adipose tissue populations of macrophages and regulatory T-lymphocytes (T(reg)) were thereafter assessed. Despite similar weight (43.8 ± 1.0 and 40.2 ± 1.5 g, respectively), male but not female mice developed hyperinsulinemia on HFD as previously described (2.5 ± 0.7 and 0.5 ± 0.1 pmol/l, respectively) consistent with glucose intolerance. Male mice also exhibited hypertrophic islets with intact function in terms of insulin release and blood perfusion. Low-grade, systemic inflammation was absent in obese female but present in obese male mice (IL-6 and mKC, males: 77.4 ± 17 and 1795 ± 563; females: 14.6 ± 4.9 and 240 ± 22 pg/ml), and the population of inflammatory macrophages was increased in intra-abdominal adipose tissues of high-fat-fed male but not female mice. In contrast, the anti-inflammatory T(reg) cell population increased in the adipose tissue of female mice in response to weight gain, while the number decreased in high-fat-fed male mice. In conclusion, female mice are protected against HFD-induced metabolic changes while maintaining an anti-inflammatory environment in the intra-abdominal adipose tissue with expanded T(reg) cell population, whereas HFD-fed male mice develop adipose tissue inflammation, glucose intolerance, hyperinsulinemia, and islet hypertrophy.