Role of macrophage chemoattractant protein-1 in acute inflammation after lung contusion.

Lung contusion (LC), commonly observed in patients with thoracic trauma is a leading risk factor for development of acute lung injury/acute respiratory distress syndrome. Previously, we have shown that CC chemokine ligand (CCL)-2, a monotactic chemokine abundant in the lungs, is significantly elevated in LC. This study investigated the nature of protection afforded by CCL-2 in acute lung injury/acute respiratory distress syndrome during LC, using rats and CC chemokine receptor (CCR) 2 knockout (CCR2(-/-)) mice. Rats injected with a polyclonal antibody to CCL-2 showed higher levels of albumin and IL-6 in the bronchoalveolar lavage and myeloperoxidase in the lung tissue after LC. Closed-chest bilateral LC demonstrated CCL-2 localization in alveolar macrophages (AMs) and epithelial cells. Subsequent experiments performed using a murine model of LC showed that the extent of injury, assessed by pulmonary compliance and albumin levels in the bronchoalveolar lavage, was higher in the CCR2(-/-) mice when compared with the wild-type (WT) mice. We also found increased release of IL-1ß, IL-6, macrophage inflammatory protein-1, and keratinocyte chemoattractant, lower recruitment of AMs, and higher neutrophil infiltration and phagocytic activity in CCR2(-/-) mice at 24 hours. However, impaired phagocytic activity was observed at 48 hours compared with the WT. Production of CCL-2 and macrophage chemoattractant protein-5 was increased in the absence of CCR2, thus suggesting a negative feedback mechanism of regulation. Isolated AMs in the CCR2(-/-) mice showed a predominant M1 phenotype compared with the predominant M2 phenotype in WT mice. Taken together, the above results show that CCL-2 is functionally important in the down-modulation of injury and inflammation in LC.

Multi-channeled biodegradable polymer/CultiSpher composite nerve guides.

Innovative methods to fabricate porous, biodegradable conduits were developed to produce nerve guides with multiple longitudinally aligned channels. The geometry of the nerve guide's channels was designed to be appropriate for harboring neurite extension. Both the coated mandrel and mandrel adhesion techniques permit flexibility in the number of channels, channel organization, and channel diameters. In this study, the composite nerve guides were comprised of poly(caprolactone) (PCL) and porous collagen-based beads (CultiSphers). The incorporation of the collagenous beads results in enhanced cortical neuron adhesion, viability, and neurite extension as compared to PCL alone. Additionally, Schwann cell studies indicated that the PCL/CultiSpher composite is a suitable substrate for cell adhesion. Mechanical properties of the PCL/CultiSpher material and in vitro degradation rates indicate the potential usefulness of this novel composite for use in the fabrication of nerve guides.