A number of novel chemotactic cytokines are becoming increasingly recognized as important participants in the elicitation specific inflammatory cells from peripheral blood to sites inflammation. Recent observations have now demonstrated that certain possess specificity for selected movement individual immune/inflammatory cell populations. One more studied is a neutrophil factor identified interleukin-8 (IL-8). This polypeptide mediator produced abundance by mononuclear phagocytic cells, well...

Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, identification novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models (canine murine) human detected significant expression pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with pathophysiology. These results were validated by real-time polymerase chain reaction immunohistochemistry studies, PBEF protein levels significantly...

Many acute and chronic lung diseases are characterized by the presence of increased numbers activated macrophages. These macrophages derived predominantly from newly recruited peripheral blood monocytes may play a role in amplification perpetuation an initial insult. The process inflammatory cell recruitment is poorly understood, although expression cell-specific chemoattractants subsequent generation chemotactic gradients likely involved. Although immune cells such as lymphocytes known to...

We investigated how complement activation promotes tissue injury and organ dysfunction during acute inflammation. Three models of lung (ALI) induced by LPS, IgG immune complexes, or C5a were used in C57BL/6 mice, all requiring availability both receptors (C5aR C5L2) for full development ALI. Ligation C5aR C5L2 with triggered the appearance histones (H3 H4) bronchoalveolar lavage fluid (BALF). BALF from humans ALI contained H4 histone. Histones absent control healthy volunteers. In mice ALI,...

We tested the hypothesis that, during sepsis, balance of pro- and anti-inflammatory cytokines is related to severity survival. Cecal ligation puncture (CLP) with a large (18-gauge)-, intermediate (21-gauge)-, or small (26-gauge)-diameter needle, sham laparotomy, was performed on outbred CD-1 mice. Concentrations tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), cytokine IL-10 were measured (by enzyme-linked immunosorbent assay) in serum, peritoneal lavage fluid, liver lung...

ABSTRACT Quorum-sensing systems are critical regulators of the expression virulence factors various organisms, including Pseudomonas aeruginosa . Las and Rhl two major quorum-sensing components, they regulated by their corresponding autoinducers, N -3-oxododecanoyl homoserine lactone (3-oxo-C 12 -HSL) -butyryl- l -homoserine (C 4 -HSL). Recent progress has demonstrated potential molecules, especially 3-oxo-C -HSL, for modulation host immune system. Here we show specific ability -HSL to...

To explore the mechanism of immunosuppression associated with sepsis, we developed a murine model sepsis-induced Pseudomonas aeruginosa pneumonia. CD-1 mice underwent either cecal ligation and 26-gauge needle puncture (CLP) or sham surgery, followed by intratracheal (i.t.) administration P. saline. Survival in undergoing CLP 24 h later i.t. saline was 58% 10%, respectively, whereas 95% animals surgery survived. Increased mortality CLP/P. group attributable to markedly impaired lung bacterial...

Abstract The overzealous production of pro-inflammatory cytokines during endotoxemia can result in shock, multiorgan dysfunction, and even death. extent tissue injury that occurs is determined not only by the release cytokines, but also expression endogenous counter-regulatory such as IL-10. In this study, we defined role endogenously-produced IL-10 a murine model endotoxemia. Initial studies indicated LPS administration to mice i.p. induces significant time-dependent increase plasma Passive...

ABSTRACT Pulmonary infection due to Pseudomonas aeruginosa has emerged as a leading cause of mortality. A vigorous host response is required effectively clear the organisms from lungs. This defense dependent on recruitment and activation neutrophils macrophages. family chemotactic cytokines (chemokines) been shown participate in this protective response. In study, we assessed role ELR + (glutamic acid-leucine-arginine motif positive) CXC chemokines their chemokine receptor (CXCR2) lung...

Transforming growth factor-β (TGF-β) induces epithelial-mesenchymal transition (EMT) of epithelial cells in both normal embryonic development and certain pathological contexts. Here, we show that TGF-β induced-EMT human lung cancer (A549; adenocarcinoma cells) mediates tumor cell migration invasion phenotypes. To gain insights into molecular events during EMT, employed a global stable isotope labeled profiling strategy using iTRAQ reagents, followed by 2DLC−MS/MS, which identified total 51...

The overzealous production of proinflammatory cytokines in sepsis can result shock, multiorgan dysfunction, and even death. In this study, we assessed the role monocyte chemoattractant protein-1 (MCP-1) as a mediator endotoxin-challenged mice. Intraperitoneal administration LPS to CD-1 mice induced substantial time-dependent increase MCP-1 plasma, lung, liver. passive immunization with rabbit antimurine antiserum 2 h before endotoxin resulted striking LPS-induced mortality from 10% control...

To study the in vivo role of alveolar macrophages (AM) gram-negative bacterial pneumonia mice, AM were eliminated by intratracheal (i.t.) administration dichloromethylene diphosphonate encapsulated liposomes. Subsequently, AM-depleted mice infected i.t. with 100 CFU Klebsiella pneumoniae, and effects depletion on survival, clearance, neutrophil (polymorphonuclear leukocyte [PMN]) recruitment assessed. It was shown that decreases survival dramatically, 100% lethality at day 3 postinfection,...

The role of macrophage inflammatory protein-2 (MIP-2) in bacterial pneumonia was characterized. Mice were challenged with Klebsiella pneumoniae intratracheally, and organs harvested at 8, 24, 48 h. Inoculation K. resulted the time-dependent expression MIP-2 mRNA protein within lung, which maximal h after inoculation. then passively immunized rabbit anti-murine serum intraperitoneally 2 before administration pneumoniae. Treatment anti-MIP-2 a 60% decrease lung neutrophil (PMNL) influx...

Invasive pulmonary aspergillosis is a devastating complication of immunosuppression, which occurs in association with neutrophil dysfunction or deficiency. ELR+ CXC chemokines are subfamily that play critical role chemotaxis and activation both vitro vivo. We hypothesized interaction these ligands chemokine receptor-2 (CXCR2), their sole murine receptor, major component neutrophil-dependent host defense against Aspergillus fumigatus. In immunocompetent animals, neutrophils were recruited to...

Abstract Invasive pulmonary aspergillosis is a common and devastating complication of immunosuppression, whose incidence has increased dramatically in tandem with the increase number immunocompromised patients. Given role TNF-α other infections, we hypothesized that an important proximal signal murine invasive aspergillosis. Intratracheal challenge Aspergillus fumigatus conidia both neutropenic (cyclophosphamide-treated) nonneutropenic BALB/c mice resulted time-dependent lung levels, which...

Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic experimental animals display "deactivated" phenotype, characterized by impaired inflammatory antimicrobial responses, including hyporesponsiveness LPS. We investigated the role LPS/TLR4 axis its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), modulating immunosuppression sepsis using murine model...

Abstract Cryptococcus neoformans is acquired via the respiratory tract and leading cause of fatal mycosis in AIDS. Development a T cell-mediated pulmonary inflammatory response critical for clearance this pathogen; however, chemotactic factors that mediate cell recruitment into lungs have not been identified. In present study, bronchoalveolar lavage (BAL) fluid levels C-C chemokine monocyte protein-1 (MCP-1) cells both increased following infection with C. neoformans. The kinetics MCP-1...

Abstract The contribution of neutrophils to lethal sensitivity and cytokine balance governing T1 T2 host responses was assessed in a murine model Legionella pneumophila pneumonia. Neutrophil depletion by administration granulocyte-specific mAb RB6-8C5 at 1 day before infection rendered mice ∼100-fold more susceptible pneumonia induced L. pneumophila. However, this treatment did not alter early bacterial clearance, despite substantial decrease neutrophil influx time point. Cytokine profiles...

The alveolar macrophage (AMO) in its pivotal position for pulmonary host defense may play a prominent role the orchestration of polymorphonuclear leukocyte (PMN) diapedesis. We demonstrate that hu- man AMO participate these inflammatory events through production novel neutrophil chemotactic factor, interleukin-8 (IL-8). induction AMO-derived IL-8 by tumor necrosis factor (TNF), lipopolysaccharide (LPS), and interleukin-1 (IL-1β) was shown to be both dose time depen- dent. Maximal gene...