SUMMARY
Neutrophil recruitment to inflammation sites purportedly depends on sequential waves of chemoattractants. Current models propose that leukotriene B4 (LTB4), a secondary chemoattractant secreted by neutrophils in response to primary chemoattractants such as formyl-peptides, is important in initiating the inflammation process. In this study, we demonstrate that LTB4 plays a central role in neutrophil activation and migration to formyl-peptides. We show that LTB4 production dramatically amplifies formyl-peptide-mediated neutrophil polarization and chemotaxis by regulating specific signaling pathways acting upstream of actin polymerization and MyoII phosphorylation. Importantly, by analyzing the migration of neutrophils isolated from wild-type mice and mice lacking the formyl peptide receptor 1, we demonstrate that LTB4 acts as a signal to relay information from cell-to-cell over long distances. Together, our findings imply that LTB4 is a signal relay molecule that exquisitely regulates neutrophils chemotaxis to formyl peptides, which are produced at the core of inflammation sites.
Raman microspectroscopy can provide the chemical contrast needed to characterize the complex intracellular environment and macromolecular organization in cells without exogenous labels. It has shown a remarkable ability to detect chemical changes underlying cell differentiation and pathology-related chemical changes in tissues but has not been widely adopted for imaging, largely due to low signal levels. Broadband coherent anti-Stokes Raman scattering (B-CARS) offers the same inherent chemical contrast as spontaneous Raman but with increased acquisition rates. To date, however, only spectrally resolved signals from the strong CH-related vibrations have been used for CARS imaging. Here, we obtain Raman spectral images of single cells with a spectral range of 600-3200 cm⁻¹, including signatures from weakly scattering modes as well as CH vibrations. We also show that B-CARS imaging can be used to measure spectral signatures of individual cells at least fivefold faster than spontaneous Raman microspectroscopy and can be used to generate maps of biochemical species in cells. This improved spectral range and signal intensity opens the door for more widespread use of vibrational spectroscopic imaging in biology and clinical diagnostics.
New and interesting properties can be obtained from macromolecular architectures functionalized with supramolecular moieties, particularly metal-ligand complexes. Self-assembly, based on the selective control of noncovalent interactions, guides the creation of hierarchically ordered materials providing access to novel structures and new properties. This field has expanded significantly in the last two decades, and one of the most ubiquitous functionalities is terpyridine. Despite its wide-spread use, much basic knowledge regarding the binding of terpyridine with metal ions remains unknown. Here, the binding constants of PEG-substituted terpyridine in relation to other literature reports are studied and a few examples of supramolecular materials from our laboratory are summarized.
Poly(l-lactic acid-b-ethylene oxide-b-l-lactic acid) (PLLA-b-PEO-b-PLLA) triblock copolymers
were synthesized by a ring-opening polymerization. PLLA and PEO sequentially crystallized by slowly
cooling (−2 °C/min) from the melt. In the resultant spherulitic morphology, the retardation of polarized
light was additive, and the sign of the spherulite (negative) was preserved when the PEO crystallized
within the framework established by the PLLA crystals. Homopolymer blends of PLLA and PEO having
the same composition as the block copolymer showed similar optical behavior. However, the change in
the optical retardation upon crystallization of the PEO was much greater for the triblock copolymer than
for the blend. Upon heating, the small-angle X-ray scattering from both the triblock copolymer and
homopolymer mixture showed a stepwise increase in the long period at ∼60 °C, i.e., when the PEO crystals
melted. For comparable volume fractions (φPLLA = 0.57), the increase in long period was greater for the
triblock copolymer than for the blend. Wide-angle X-ray diffraction studies on shear aligned triblock
copolymers indicate that the PLLA and PEO crystals adopt the same average orientation; though, in the
case of the copolymer, the orientation is more strongly coupled.
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