Exercise-recruited NK cells display exercise-associated eHSP-70

It is hypothesized that increased plasma or serum concentrations of extracellular heat shock proteins (eHSP) serve as a danger signal to the innate immune system. Cellular binding of eHSP leads to activation of NK cells and monocytes, as measured by their increased cytokine production, mitotic division and killing capacity. We examined whether eHSP binds to NK lymphocytes in vivo in athletes performing endurance exercise in the heat. Eighteen trained male runners ran at 70% VO2max at 35 degrees C and 40% relative humidity. Venous blood collected before, after and 1.5 h after exercise was analysed for leukocyte distribution, phenotype and eHSP70. NK cell-enriched samples were examined for co-localization of CD94 and eHSP70 expression. Plasma eHSP-70 concentration was measured by ELISA. Subjects ran for approximately 50 min, which elicited a reversible leukocytosis. NK cell count increased 83% (p < 0.01) immediately after exercise, then decreased to 66% of the resting level 1.5 h after exercise (p < 0.05). Plasma eHSP concentration increased 167% after exercise and remained elevated (by up to 71%) 1.5 h after exercise (p < 0.01). eHSP was expressed on both NK cells and monocytes at all times; the count of NK cells positive for eHSP doubled from 0.04 +/- 0.02 10(9)/L (mean +/- SD) to 0.08 +/- 0.06 10(9)/L after exercise. In summary, exercise in the heat increased free plasma eHSP concentration, and the eHSP co-localized with CD94 on NK cells. These data confirm the link between exercise and activation of the innate immune system.

Diverse populations of T cells with NK cell receptors accumulate in the human intestine in health and in colorectal cancer

T cells expressing NK cell receptors (NKR) display rapid MHC-unrestricted cytotoxicity and potent cytokine secretion and are thought to play roles in immunity against tumors. We have quantified and characterized NKR+ T cells freshly isolated from epithelial and lamina propria layers of duodenum and colon from 16 individuals with no evidence of gastrointestinal disease and from tumor and uninvolved tissue from 19 patients with colorectal cancer. NKR+ T cell subpopulations were differentially distributed in different intestinal compartments, and CD161+ T cells accounted for over one half of T cells at all locations tested. Most intestinal CD161+ T cells expressed alpha beta TCR and either CD4 or CD8. Significant proportions expressed HLA-DR,CD69 and Fas ligand. Upon stimulation in vitro, CD161+ T cells produced IFN-gamma and TNF-alpha but not IL-4. NKT cells expressing the Valpha24Vbeta11 TCR, which recognizes CD1d,were virtually absent from the intestine, but colonic cells produced IFN-gamma in response to the NKT cell agonist ligand alpha-galactosylceramide. NKR+ T cells were not expanded in colonic tumors compared to adjacent uninvolved tissue. The predominance, heterogeneity and differential distribution of NKR+ T cells at different intestinal locations suggests that they are central to intestinal immunity.

Tutorial on NK model

NK model, proposed by Kauffman (1993), is a strong simulation framework to study competing dynamics. It has been applied in some social science fields, for instance, organization science. However, like many other simulation methods, NK model has not received much attention from Management Information Systems (MIS) discipline. This tutorial, thus, is trying to introduce NK model in a simple way and encourage related studies. To demonstrate how NK model works, this tutorial reproduces several Levinthal’s (1997) experiments. Besides, this tutorial attempts to make clear the relevance between NK model and agent-based modeling (ABM). The relevance can be a theoretical basis to further develop NK model framework for other research scenarios. For example, this tutorial provides an NK model solution to study IT value cocreation process by extending network structure and agent interactions.

Simulation design in information systems research: example of studying it value cocreation with NK model

As an emerging research method that has showed promising potential in several research disciplines, simulation received relatively few attention in information systems research. This paper illustrates a framework for employing simulation to study IT value cocreation. Although previous studies identified factors driving IT value cocreation, its underlying process remains unclear. Simulation can address this limitation through exploring such underlying process with computational experiments. The simulation framework in this paper is based on an extended NK model. Agent-based modeling is employed as the theoretical basis for the NK model extensions.

Human papillomavirus DNA detected in peripheral blood samples from healthy Australian male blood donors

Recent studies have shown that human papillomavirus (HPV) DNA can be found in circulating blood, including peripheral blood mononuclear cells (PBMCs), sera, plasma, and arterial cord blood. In light of these findings, DNA extracted from PBMCs from healthy blood donors were examined in order to determine how common HPV DNA is in blood of healthy individuals. Blood samples were collected from 180 healthy male blood donors (18-76 years old) through the Australian Red Cross Blood Services. Genomic DNA was extracted and specimens were tested for HPV DNA by PCR using a broad range primer pair. Positive samples were HPV-type determined by cloning and sequencing. HPV DNA was found in 8.3% (15/180) of the blood donors. A wide variety of different HPV types were isolated from the PBMCs; belonging to the cutaneous beta and gamma papillomavirus genera and mucosal alpha papillomaviruses. High-risk HPV types that are linked to cancer development were detected in 1.7% (3/180) of the PBMCs. Blood was also collected from a healthy HPV-positive 44-year-old male on four different occasions in order to determine which blood cell fractions harbor HPV. PBMCs treated with trypsin were negative for HPV, while non-trypsinized PBMCs were HPV-positive. This suggests that the HPV in blood is attached to the outside of blood cells via a protein-containing moiety. HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission.

Mechanism of p-nitrophenol adsorption from aqueous solution by HDTMA+-pillared montmorillonite : implications for water purification

HDTMA+ pillared montmorillonites were obtained by pillaring different amounts of the surfactant hexadecyltrimethylammonium bromide (HDTMAB) into sodium montmorillonite (Na-Mt) in an aqueous solution. The optimum conditions and batch kinetics of sorption of p-nitrophenol from aqueous solutions were reported. The solu-tion pH had a very important effect on the sorption of p-nitrophenol. The maximum p-nitrophenol absorption/adsorption occurs when solution pH (7.15~7.35) is approx-imately equal to the pKa (7.16) of the p-nitrophenol ion deprotonation reaction. X-ray diffraction analysis showed that surfactant cations had been pillared into the interlayer and the p-nitrophenol affected the arrangement of surfactant. With the increased con-centration of surfactant cations, the arrangement of HDTMA+ within the clay inter-layer changes and the sorption of p-nitrophenol increases. HDTMA+ pillared mont-morillonites are more effective than Na-Mt for the adsorption of p-nitrophenol from aqueous solutions. The Langmuir, Freundlich and dual-mode sorption were tested to fit the sorption isotherms.

IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms

Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4+ and CD8+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1−/− mice or in mice depleted of CD4+ and/or CD8+ cells than in normal mice. The tumors in RAG1−/− mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

The open window of susceptibility to infection after acute exercise in healthy young male elite athletes

The 'open window' theory is characterised by short term suppression of the immune system following an acute bout of endurance exercise. This window of opportunity may allow for an increase in susceptibility to upper respiratory illness (URI). Many studies have indicated a decrease in immune function in response to exercise. However, many studies do not indicate changes in immune function past 2 hours after the completion of exercise, consequently failing to determine whether these immune cells numbers, or importantly their function, return to resting levels before the start of another bout of exercise. Ten male 'A' grade cyclists (age 24.2 +/- 5.3 years; body mass 73.8 +/- 6.5 kg; VO(2peak) 65.9 +/- 7.1 mL.kg(-1).min(-1)) exercised for two hours at 90% of their second ventilatory threshold. Blood samples were collected pre-, immediately post-, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours post-exercise. Immune variables examined included total leukocyte counts, neutrophil function (oxidative burst and phagocytic function), lymphocyte subset counts (CD4(+), CD8(+), and CD16(+)/56(+)), natural killer cell activity (NKCA), and NK phenotypes (CD56(dim)CD16(+), and CD56(bright)CD16(-)). There was a significant increase in total lymphocyte numbers from pre-, to immediately post-exercise (p<0.01), followed by a significant decrease at 2 hours post-exercise (p<0.001). CD4(+) T-cell counts significantly increased from pre-exercise, to 4 hours post- (p<0.05), and 6 hours post-exercise (p<0.01). However, NK (CD16(+)/56(+)) cell numbers decreased significantly from pre-exercise to 4 h post-exercise (p<0.05), to 6 h post-exercise (p<0.05), and to 8 h post-exercise (p<0.01). In contrast, CD56(bright)CD16- NK cell counts significantly increased from pre-exercise to immediately post-exercise (p<0.01). Neutrophil oxidative burst activity did not significantly change in response to exercise, while neutrophil cell counts significantly increased from pre-exercise, to immediately post-exercise (p<0.05), and 2 hours post-exercise (p<0.01), and remained significantly above pre-exercise levels to 8 hours post-exercise (p<0.01). Neutrophil phagocytic function significantly decreased from 2 hours post-exercise, to 6 hours post- (p<0.05), and 24 hours post-exercise (p<0.05). Finally, eosinophil cell counts significantly increased from 2 hours post to 6 hours post- (p<0.05), and 8 hours post-exercise (p<0.05). This is the first study to show changes in immunological variables up to 8 hours post-exercise, including significant NK cell suppression, NK cell phenotype changes, a significant increase in total lymphocyte counts, and a significant increase in eosinophil cell counts all at 8 hours post-exercise. Suppression of total lymphocyte counts, NK cell counts and neutrophil phagocytic function following exercise may be important in the increased rate of URI in response to regular intense endurance training.

TLR2, but Not TLR4, is required for effective host defence against Chlamydia respiratory tract infection in early life

Chlamydia pneumoniae commonly causes respiratory tract infections in children, and epidemiological investigations strongly link infection to the pathogenesis of asthma. The immune system in early life is immature and may not respond appropriately to pathogens. Toll-like receptor (TLR)2 and 4 are regarded as the primary pattern recognition receptors that sense bacteria, however their contribution to innate and adaptive immunity in early life remains poorly defined. We investigated the role of TLR2 and 4 in the induction of immune responses to Chlamydia muridarum respiratory infection, in neonatal wild-type (Wt) or TLR2-deficient (−/−), 4−/− or 2/4−/− BALB/c mice. Wt mice had moderate disease and infection. TLR2−/− mice had more severe disease and more intense and prolonged infection compared to other groups. TLR4−/− mice were asymptomatic. TLR2/4−/− mice had severe early disease and persistent infection, which resolved thereafter consistent with the absence of symptoms in TLR4−/− mice. Wt mice mounted robust innate and adaptive responses with an influx of natural killer (NK) cells, neutrophils, myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells, and activated CD4+ and CD8+ T-cells into the lungs. Wt mice also had effective production of interferon (IFN)γ in the lymph nodes and lung, and proliferation of lymph node T-cells. TLR2−/− mice had more intense and persistent innate (particularly neutrophil) and adaptive cell responses and IL-17 expression in the lung, however IFNγ responses and T-cell proliferation were reduced. TLR2/4−/− mice had reduced innate and adaptive responses. Most importantly, neutrophil phagocytosis was impaired in the absence of TLR2. Thus, TLR2 expression, particularly on neutrophils, is required for effective control of Chlamydia respiratory infection in early life. Loss of control of infection leads to enhanced but ineffective TLR4-mediated inflammatory responses that prolong disease symptoms. This indicates that TLR2 agonists may be beneficial in the treatment of early life Chlamydia infections and associated diseases.

Helsinki adventure : inside the ‘design nation’

A travel article about Helsinki exploring the city's design culture. I’M often told that I’m from Finland. Even those who’ve known me for years confuse it with my birthplace, which is, in fact, Iceland. I’m not sure why the two countries are mixed up in this way, but it might be that Iceland and Finland are, in a sense, the “other” Scandinavian nations – on different sides of the Nordic world, but in the mind joined as its outer borders...

After the flood

FRUSTRATED residents of Grantham, the Lockyer Valley township devastated by Queensland's deadly summer floods, are demanding that the commission of inquiry into the disaster investigate whether an earth wall around a sand quarry helped cause the "inland tsunami" that killed 12 people and destroyed scores of homes.

Perfect start to a river cruise

A travel article about Amsterdam. BY COINCIDENCE, I flew to Amsterdam a week after I'd read Ian McEwan's novel of the same name. Amsterdam is a modern take on the theme of duelling and, in many ways, he couldn't have chosen a more appropriate place for his title. This is a city that duels with itself. I flew in at dawn, traditionally the moment to test your abilities at 10 paces. The countryside below was dark but blocks of orange light pulsed in the fields...

Grandad falsely accused of rape and incest

THE Queensland Department of Child Safety has refused for 18 months to correct a file that falsely accused a man from Toowoomba of being a rapist who was jailed for fathering his own grandchild.

Mustering a wild bunch

A travel article about the South Dakota Governor's annual Buffalo Roundup Publication title: "Saddle up for South Dakota Governor Buffalo Roundup" “The crowd always cheers for the buffalo,” says Linda Daugaard, wife of the South Dakota governor. Up to now she and I have been talking about life in the state and her role, as its First Lady, in promoting youth literacy and other programs for families and children...