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Closed circulatory systems (CCS) underlie the function of vertebrate organs, but in long bones their structure is unclear, although they constitute the exit route for bone marrow (BM) leukocytes. To understand neutrophil emigration from BM, we studied the vascular system of murine long bones. Here we show that hundreds of capillaries originate in BM, cross murine cortical bone perpendicularly along the shaft and connect to the periosteal circulation. Structures similar to these trans-cortical-vessels (TCVs) also exist in human limb bones. TCVs express arterial or venous markers and transport neutrophils. Furthermore, over 80% arterial and 59% venous blood passes through TCVs. Genetic and drug-mediated modulation of osteoclast count and activity leads to substantial changes in TCV numbers. In a murine model of chronic arthritic bone inflammation, new TCVs develop within weeks. Our data indicate that TCVs are a central component of the CCS in long bones and may represent an important route for immune cell export from the BM.

Papillon-Lefèvre syndrome (PLS) is characterized by nonfunctional neutrophil serine proteases (NSPs) and fulminant periodontal inflammation of unknown cause. Here we investigated neutrophil extracellular trap (NET)-associated aggregation and cytokine/chemokine-release/degradation by normal and NSP-deficient human and mouse granulocytes. Stimulated with solid or soluble NET inducers, normal neutrophils formed aggregates and both released and degraded cytokines/chemokines. With increasing cell density, proteolytic degradation outweighed release. Maximum output of cytokines/chemokines occurred mostly at densities between 2 × 10 and 4 × 10 neutrophils/cm. Assessment of neutrophil density in vivo showed that these concentrations are surpassed during inflammation. Association with aggregated NETs conferred protection of neutrophil elastase against α1-antitrypsin. In contrast, eosinophils did not influence cytokine/chemokine concentrations. The proteolytic degradation of inflammatory mediators seen in NETs was abrogated in Papillon-Lefèvre syndrome (PLS) neutrophils. In summary, neutrophil-driven proteolysis of inflammatory mediators works as a built-in safeguard for inflammation. The absence of this negative feedback mechanism might be responsible for the nonresolving periodontitis seen in PLS.-Hahn, J., Schauer, C., Czegley, C., Kling, L., Petru, L., Schmid, B., Weidner, D., Reinwald, C., Biermann, M. H. C., Blunder, S., Ernst, J., Lesner, A., Bäuerle, T., Palmisano, R., Christiansen, S., Herrmann, M., Bozec, A., Gruber, R., Schett, G., Hoffmann, M. H. Aggregated neutrophil extracellular traps resolve inflammation by proteolysis of cytokines and chemokines and protection from antiproteases.

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Abstract:We investigate the chiroptical response of a single plasmonic nanohelix interacting with a weakly focused circularly polarized Gaussian beam. The optical scattering at the fundamental resonance is characterized experimentally and numerically. The angularly resolved scattering of the excited nanohelix is verified experimentally and it validates the numerical results. We employ a multipole decomposition analysis to study the fundamental and first higher-order resonance of the nanohelix, explaining their chiral properties in terms of the formation of chiral dipoles. N. Gadegaard and M. Kadodwala, "Ultrasensitive detection and characterization of biomolecules using superchiral fields," Nat. Nanotechnol. 5, 783-787 (2010). 4. Y. Zhao, L. Xu, W. Ma, L. Wang, H. Kuang, C. Xu and N. A. Kotov, "Shell-engineered chiroplasmonic assemblies of nanoparticles for zeptomolar DNA detection," Nano Lett. 14(7), 3908-3913 (2014). 5. C. Jack. A. S. Karimullah, R. Leyman, R. Tullius, V. M. Rotello, G. Cooke, N. Gadegaard, L. D. Barron and M.Kadodwala, "Biomacromolecular stereostructure mediates mode hybridization in chiral plasmonic nanostructures," Nano Lett. 16(9), 5806-5814 (2016

We show how optical phonons can be used as efficient probes in self-organized Si1−xGex islands grown on Si(001). Both the alloy composition and residual strain in the islands were originally determined from the phonon frequencies and Raman intensities. The experimental results are in good agreement with the strain relaxation simulated by means of the finite element method.