Journal of leukocyte biology
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Comparative Study
Human epidermal Langerhans cells differ from monocyte-derived Langerhans cells in CD80 expression and in secretion of IL-12 after CD40 cross-linking.
Langerhans cells (LCs) represent an immature population of myeloid dendritic cells (DCs). As a result of their unique Birbeck granules (BGs), langerin expression, and heterogeneous maturation process, they differ from other immature DCs. Monocyte-derived LCs (MoLCs) mimic epidermal LCs. ⋯ These data indicate that MoLCs as well as LCs display no maturation arrest concerning CD83 and CD86 expression. In difference to MoLCs, LCs resisted activation by CD40L and LPS in terms of IL-12 production. This shows that natural and generated LCs share similar features but differ in relevant functions.
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Thermal injury induces an inflammatory response that contributes to the development of secondary tissue damage. Neutrophil recruitment and activation are in part responsible for this tissue damage. Although gammadelta T cells have been shown to regulate the inflammatory responses in tissues that are prone to neutrophil-mediated injury post-burn, their role in the induction of secondary tissue injury post-burn remains unknown. ⋯ A parallel increase in plasma and small intestine levels of the chemokines macrophage-inflammatory protein-1beta (chemokine ligand 4) and keratinocyte-derived chemokine (CXC chemokine ligand 1) were observed in injured WT mice but not in injured gammadelta TCR-/- mice. Increased activation (CD120b expression) of the circulating gammadelta T cell population was also observed at 3 h post-burn in WT mice. These results indicate the gammadelta T cells, through the production of chemokines, play a central role in the initiation of neutrophil-mediated tissue damage post-burn.
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Polymorphonuclear neutrophil (PMN) extravasation/sequestration in the lung and a dysregulated inflammatory response characterize the pathogenesis of acute lung injury (ALI). Previously, we have shown that hemorrhage (Hem) serves to prime PMN such that subsequent septic challenge [cecal ligation and puncture (CLP)] produces a pathological, inflammatory response and consequent lung injury in mice. Keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) are murine CXC chemokines found elevated in the lungs and plasma following Hem/CLP and have been reported by others to share a common receptor (CXCR2). ⋯ KC showed a significant reduction at the 0.4 mg antileukinate dose. In contrast, plasma MIP-2 was significantly elevated at both doses compared with the PBS-treated controls. Together, these data demonstrate that blockade of CXCR2 signaling attenuates shock-induced priming and ALI observed following Hem and subsequent septic challenge in mice.
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We have previously shown that hypertonic stress (HS) can suppress chemoattractant-induced neutrophil responses via cyclic adenosine monophosphate and enhance these responses through p38 mitogen-activated protein kinase (MAPK) activation. The underlying mechanisms are unknown. Here, we report that HS dose-dependently releases adenosine 5'-triphosphate (ATP) from neutrophils and that extracellular ATP is rapidly converted to adenosine or activates p38 MAPK and enhances N-formyl-methionyl-leucyl-phenylalanine-induced superoxide formation. ⋯ A2 receptor agonists mimicked the suppressive effects of HS; the A2 receptor antagonists 8-(p-sulfophenyl)theophylline, 3,7-dimethyl-1-(2-propynyl)xanthine, 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, and 3-propylxanthine, but not A1 and A3 receptor antagonists, decreased the suppressive effect of HS, indicating that HS suppresses neutrophils via A2 receptor activation. Antagonists of P2 receptors counteracted the enhancing effects of ATP, suggesting that HS costimulates neutrophils by means of P2 receptor activation. We conclude that hypertonic stress regulates neutrophil function via a single molecule (ATP) and its metabolite (adenosine), using positive- and negative-feedback mechanisms through the activation of P2 and A2 receptors, respectively.
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Comparative Study
Eosinophil degranulation in the allergic lung of mice primarily occurs in the airway lumen.
Eosinophil degranulation is thought to play a pivotal role in the pathogenesis of allergic disorders. Although mouse models of allergic disorders have been used extensively to identify the contribution of eosinophils to disease, ultrastructural evidence of active granule disassembly has not been reported. In this investigation, we characterized the degree of eosinophil activation in the bone marrow, blood, lung tissue, and airways lumen [bronchoalveolar lavage fluid (BALF)] of ovalbumin-sensitized and aero-challenged wild-type and interleukin-5 transgenic mice. ⋯ Thus, mouse eosinophils undergo PMD during allergic inflammation, and in turn, this process may contribute to pathogenesis. However, the degranulation process in the allergic lung of mice is primarily compartmentalized to the airway lumen. Understanding the mechanism of eosinophil degranulation in the airway lumen may provide important insights into how this process occurs in human respiratory diseases.