Role of Cdk4 in lymphocyte function and allergen response.

We recently described a new adhesion pathway in lymphocytes that is dependent on Cyclin-dependent kinase (Cdk) 4 activity and mediates lymphocyte interactions with endothelial matrix. We showed that Cdk4(-/-) mice had impaired recruitment of lymphocytes following bleomycin model of acute lung injury. In this study, we characterized the development and function of hematopoietic cells in Cdk4(-/-) mice and assessed the response of Cdk4(-/-) mice to allergen challenge. Cdk4(-/-) mice had hypoplastic thymuses with decreased total thymocyte cell numbers and increased CD4/CD8 double negative cells. Cdk4(-/-) bone marrow (BM) chimeric mice showed similar findings. Thymocytes from either Cdk4(-/-) or Cdk4(-/-) BM chimeric mice proliferated equally well as wild type controls in response to IL-2 activation. However Cdk4(-/-) thymocytes had decreased adhesion to both endothelial cell matrix and fibronectin compared to wildtype (WT) controls, whereas Cdk4(-/-) and WT splenocytes had similar adhesion. When Cdk4(-/-) BM chimeric mice and wild type BM chimeric mice were sensitized and challenged by intranasal administration of ovalbumin, we found no differences in allergic responses in the lung and airways between the two groups, as measured by inflammatory cell infiltrate, airway hyperreactivity, IgE levels and cytokine levels. In summary, we show that Cdk4 plays a previously unrecognized role in thymocyte maturation and adhesion, but is not required for thymocyte proliferation. In addition, Cdk4 is not required for lymphocyte trafficking to the lung following allergen sensitization and challenge.

[Photophysical properties of poly (2-methoxy-5-octyloxy)-p-phenylene vinylene/TiO2 nano-composites].

The photoelectric composites of poly (2-methoxy-5-octyloxy)-p-phenylene vinylene/nanometer TiO2 (PMOCOPV/ TiO2) with different nanometer TiOz amount were synthesized through dehydrochlorination in-situ polymerization. The results of Fourier transform infrared spectroscopy and Raman spectroscopy indicated that the surface of nanometer TiO2 was coated with PMOCOPV. UV-Vis spectrum showed that the absorption of PMOCOPV/TiO2 nano-composites was strengthened in the range of violet and visible light with the contents of TiO2 increasing. The composite dimensions were observed by highly resolution transmission electron microscope, PMOCOPV/TiO2 nano-composites dispersed uniformly and possessed core-shell structure, the diameter of PMOCOPV/TiO2 was measured to be about 30 nm, and the thickness of the PMOCOPV coating was about 8-10 nm. Photoluminescence spectroscopy indicated that the maximum emission wavelength of the PMOCOPV/TiO2 was red-shifted with increasing TiO2 concentration. The fluorescence lifetime of PMOCOPV/TiO2 was about 1 ns. The intensity and lifetime of fluorescence was increased remarkably with the contents of TiO2 increasing. The mechanism of the strengthened fluorescence quantum efficiency and fluorescence intensity of PMOCOPV/TiO2 was investigated through the charge transfer, exciton dissociation and potential energy in PMOCOPV/TiO2 nano-composites.

Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function.

Increased lung vascular permeability is an important contributor to respiratory failure in acute lung injury (ALI). We found that a function-blocking antibody against the integrin alphavbeta5 prevented development of lung vascular permeability in two different models of ALI: ischemia-reperfusion in rats (mediated by vascular endothelial growth factor [VEGF]) and ventilation-induced lung injury (VILI) in mice (mediated, at least in part, by transforming growth factor-beta [TGF-beta]). Knockout mice homozygous for a null mutation of the integrin beta5 subunit were also protected from lung vascular permeability in VILI. In pulmonary endothelial cells, both the genetic absence and blocking of alphavbeta5 prevented increases in monolayer permeability induced by VEGF, TGF-beta, and thrombin. Furthermore, actin stress fiber formation induced by each of these agonists was attenuated by blocking alphavbeta5, suggesting that alphavbeta5 regulates induced pulmonary endothelial permeability by facilitating interactions with the actin cytoskeleton. These results identify integrin alphavbeta5 as a central regulator of increased pulmonary vascular permeability and a potentially attractive therapeutic target in ALI.