As the epidemic of gunshot injuries and firearm fatalities continues to proliferate in the United States, knowledge regarding gunshot wound (GSW) injury and management is increasingly relevant to ...health-care providers. Unfortunately, existing guidelines are largely outdated, written in a time that high-velocity weapons and deforming bullets were chiefly restricted to military use. Advances in firearm technology and increased accessibility of military grade firearms to civilians has exacerbated the nature of domestic GSW injury and complicated clinical decision-making, as these weapons are associated with increased tissue damage and often result in retained bullets. Currently, there is a lack of literature addressing recent advances in the field of projectile-related trauma, specifically injuries with retained bullets. This review aims to aggregate the available yet dispersed findings regarding ballistics, GSW etiology, and treatment, particularly for cases involving retained projectiles.
Galectin-1, a member of the family of beta-galactoside binding proteins, has growth regulatory and immunomodulatory activities. We report here that galectin-1, expressed by stromal cells in human ...thymus and lymph nodes, is present at sites of cell death by apoptosis during normal T-cell development and maturation. Galectin-1 induced apoptosis of activated human T cells and human T leukaemia cell lines. Resting T cells also bound galectin-1, but did not undergo apoptosis. Human endothelial cells that expressed galectin-1 induced apoptosis of bound T cells. Galectin-1-induced apoptosis required expression of CD45, and was decreased when N-glycan elongation was blocked by treatment of the cells by swainsonine, whereas inhibition of O-glycan elongation potentiated the apoptotic effect of galectin-1. Induction of apoptosis by an endogenous mammalian lectin represents a new mechanism for regulating the immune response.
Galectin-1 is a galactoside-binding lectin expressed in multiple tissues that has pleiotropic immunomodulatory functions. We previously showed that galectin-1 activates human monocyte-derived ...dendritic cells (MDDCs) and triggers a specific genetic program that up-regulates DC migration through the extracellular matrix, an integral property of mucosal DCs. Here, we identify the galectin-1 receptors on MDDCs and immediate downstream effectors of galectin-1-induced MDDC activation and migration. Galectin-1 binding to surface CD43 and CD45 on MDDCs induced an unusual unipolar co-clustering of these receptors and activates a dose-dependent calcium flux that is abrogated by lactose. Using a kinome screen and a systems biology approach, we identified Syk and protein kinase C tyrosine kinases as mediators of the DC activation effects of galectin-1. Galectin-1, but not lipopolysaccharide, stimulated Syk phosphorylation and recruitment of phosphorylated Syk to the CD43 and CD45 co-cluster on MDDCs. Inhibitors of Syk and protein kinase C signaling abrogated galectin-1-induced DC activation as monitored by interleukin-6 production; and MMP-1, -10, and -12 gene up-regulation; and enhanced migration through the extracellular matrix. The latter two are specific features of galectin-1-activated DCs. Interestingly, we also found that galectin-1 can prime DCs to respond more quickly to low dose lipopolysaccharide stimulation. Finally, we underscore the biological relevance of galectin-1-enhanced DC migration by showing that intradermal injection of galectin-1 in MRL-fas mice, which have a defect in skin DC emigration, increased the in vivo migration of dermal DCs to draining lymph nodes.
The biological impact of glycans is as diverse and complex as the impact of proteins on biology. Familiar roles include those as a protein folding checkpoint in the endoplasmic reticulum and as a ...modulator of the serum half-life of secreted glycoproteins, but it has become clear over the last several decades that glycans are key signaling moieties, participate in cell-cell interactions and modulate the function of individual proteins, to name but a few examples. In the immune system, the majority of microbial "patterns" are glycans or glycoconjugates, while virtually all cell surface receptors are glycoproteins, and antibody glycosylation critically influences antibody function. In order to provide a simple contextual framework to understand the myriad roles, glycans play in immunity, we propose that glycan effects are considered direct or indirect, depending on their direct participation or their indirect effects on other components in a given biological process or pathway. Here, we present the published evidence that supports this framework, which ultimately leads to the conclusion that we should learn to embrace the complexity inherent to the glycome and its potential as a largely uncharted but target rich area of new therapeutic investigation.
Multivalent protein–carbohydrate interactions regulate essential cellular events, including cell proliferation, adhesion and death. These multivalent interactions can create homogeneous complexes of ...lectins, such as the galectins, with their saccharide ligands. Lectin–saccharide complexes can concentrate specific glycoproteins or glycolipids within the lattice, while excluding other cell surface molecules. The formation of lectin–saccharide lattices on the cell surface can thus organize the plasma membrane into specialized domains that perform unique functions.
Multivalent galectins have the ability to form cross-linked lattices with glycoproteins on the cell surface. How does this process influence cell signaling, cell adhesion and cell death?
Jakarta Bay in Indonesia and its offshore island chain, the Thousand Islands, are facing extreme pollution. Surfactants and diesel-borne compounds from sewage and bilge water discharges are common ...pollutants. However, knowledge of their effects on reef fish physiology is scarce. This study investigated combined and single effects of a) the water accommodated fraction of diesel (WAF-D, determined by ƩEPA polycyclic aromatic hydrocarbons (PAHs)) and b) the surfactant linear alkylbenzene sulfonate (LAS) on metabolic performance of the coral reef fish Siganus guttatus. Responses to combinations of each pollutant with elevated temperature (+3°C) were determined. Short-term exposure to WAF-D led to a significant decrease in standard metabolic rates, while LAS led to an increase. During combined exposure, metabolic depression was observed. Effects of pollutants were not amplified by elevated temperature. This study highlights the need to reduce import of these pollutants and to avoid negative long-term effects on fish health.
•Surfactants and diesel-borne compounds were determined in Jakarta Bay and the Thousand Islands.•Exposure of Siganus guttatus to water accommodated fraction of diesel led to metabolic depression.•Exposure of Siganus guttatus to an anionic surfactant led to increased metabolic rates.•Combined exposure to both pollutants caused metabolic depression (interactive effect).•Effects of pollutants were not amplified by elevated temperature (no synergism).
Galectin-1 induces death of immature thymocytes and activated T cells. Galectin-1 binds to T cell-surface glycoproteins CD45, CD43, and CD7, although the precise roles of each receptor in cell death ...are unknown. We have determined that CD45 can positively and negatively regulate galectin-1-induced T cell death, depending on the glycosylation status of the cells. CD45(+) BW5147 T cells lacking the core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) were resistant to galectin-1 death. The inhibitory effect of CD45 in C2GnT(-) cells appeared to require the CD45 cytoplasmic domain, because Rev1.1 cells expressing only CD45 transmembrane and extracellular domains were susceptible to galectin-1 death. Moreover, treatment with the phosphotyrosine-phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate(V) enhanced galectin-1 susceptibility of CD45(+) T cell lines, but had no effect on the death of CD45(-) T cells, indicating that the CD45 inhibitory effect involved the phosphatase domain. Expression of the C2GnT in CD45(+) T cell lines rendered the cells susceptible to galectin-1, while expression of the C2GnT in CD45(-) cells had no effect on galectin-1 susceptibility. When CD45(+) T cells bound to galectin-1 on murine thymic stromal cells, only C2GnT(+) T cells underwent death. On C2GnT(+) cells, CD45 and galectin-1 co-localized in patches on membrane blebs while no segregation of CD45 was seen on C2GnT(-) T cells, suggesting that oligosaccharide-mediated clustering of CD45 facilitated galectin-1-induced cell death.
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the beta-cells of the pancreas. We investigated the ability of soluble galectin-1 (gal-1), an endogenous lectin that ...promotes T cell apoptosis, to down-regulate the T cell response that destroys the pancreatic beta-cells. We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of beta-cell-reactive T cells. Administration of gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical stages of T1D. Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4(+) T cells with content of IL-4, IL-5, or IL-10. The beneficial effects of gal-1 correlated with the ability of the lectin to trigger apoptosis of the T cell subsets that cause beta-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly, gal-1 reversed beta-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not cause major side effects or beta-cell toxicity in NOD mice, the use of gal-1 to control beta-cell autoimmunity represents a novel alternative for treatment of subclinical or ongoing T1D.
PDF
