Mitochondrial DNA mutations were assessed in single muscle

fibres using Real-time PCR. We identified respiratory-deficient fibres at different stages of mitochondrial dysfunction, with downregulated expression of complex I of mitochondrial respiratory chain being the initial feature. We detected mitochondrial DNA rearrangements in the majority of individual respiratory-deficient muscle fibres. There was a strong correlation between number of T lymphocytes Tyrosine Kinase Inhibitor Library and macrophages residing in muscle tissue and the abundance of respiratory-deficient fibres. Moreover, we found that respiratory-deficient muscle fibres were more likely to be atrophic compared to respiratory-normal counterparts. Our findings suggest that mitochondrial dysfunction has a role in sIBM progression. A strong correlation between the severity of inflammation, degree of mitochondrial changes and atrophy implicated existence of a mechanistic link between these three parameters. We propose Smoothened Agonist a role for inflammatory cells in the initiation of mitochondrial DNA damage, which when accumulated, causes respiratory dysfunction, fibre atrophy and ultimately degeneration

of muscle fibres. “
“While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical Methane monooxygenase target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas. We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset).

We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre-Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem. Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre-Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic CJD, we suggest that these nuclei represent key clinical target areas in prion diseases. “
“L. E. Taylor, Y. J. Kaminoh, C. K. Rodesch and K. M.

, 1999; Decker et al., 2000; Weeratna et al., 2000; Near selleck et al., 2002). In this study, we expressed the early antigen Ag85b and the late-stage antigen HspX of H37Rv, combined this mixture of these two proteins with another previously prepared recombinant fusion protein

CFP-10:ESAT-6 (C/E) (Waters et al., 2004) (W.-X. Du, B.-W. Chen, X.-B. Shen, C. Su & G.-Z. Wang, unpublished data) and developed a vaccine regimen that incorporates aluminum and CpG DNA, both of which are currently being evaluated in veterinary and human vaccines as adjuvants. The immune response to the vaccine was evaluated in mice, and its therapeutic effectiveness was evaluated in Mtb-challenged guinea pigs. The results showed that the three antigens with CpG and aluminum adjuvants trigger strong humoral and cellular immune responses in mice but play only a small role in control of the disease in Mtb-challenged guinea pigs. Seventy-two Hartley guinea pigs (36 female, 36 male, weighing 250–300 g) were purchased from the Experimental Animal Center of National Institute for the Control of Pharmaceutical and Biological Products (NICPBP) and temporarily kept under barrier conditions in a biosafety level III animal laboratory. Thirty-six BALB/c mice, aged 6–8 weeks, were obtained PF-01367338 concentration from NICPBP and temporarily maintained under specific pathogen-free conditions. All animals used in this study

were treated according to the standards of animal welfare and reviewed by the Animal Care & Welfare

Committee of NICPBP. The nucleotide sequences of Ag85b and HspX of Mtb H37Rv were obtained from GenBank (gene ID: 885785 and 887579). The Mtb H37Rv strain (ATCC35801) was obtained from the Mycobacterium Laboratory of NICPBP. Primers for Ag85b and HspX are as follows: upstream primer for Ag85b, 5′-CACGCATATGACAGACGTGAGCC-3′ (underlined sequence is restriction site of NdeI), downstream primer for Ag85b, 5′-TTGAATTCTCAGCCGGCGCCT-3′ (the underlined sequence is an EcoRI site); upstream primer for HspX, 5′-TTCATCATATGGCCACCACCCT-3′ (the underlined sequence is an NdeI site), downstream primer for HspX, P2, 5′-GTGCAAGCTTTCAGTTGGTGGAC-3′ (the underlined sequence is a HindIII site). After amplification and double digestion, Diflunisal the PCR products were individually ligated into pET30a (Merck, Darmstadt, Germany). The recombinant plasmids were transformed into Escherichia coli DH5α cells and sequenced to confirm the insertion (Invitrogen, Shanghai, China). All the enzymes were purchased from TaKaRa Biotechnology Co. Ltd (Dalian, China). After successful transformation of recombinant plasmids from DH5α into E. coli BL21-competent cells (BioRev-Tech. Scientific & Technical Co. Ltd, Beijing, China), rAg85b and rHspX were purified from a 2 L Luria–Bertani culture and incubated at 37 °C for 4 h or until the OD600 nm reached 0.6 in the presence of 1 mM isopropyl thiogalactoside (Sigma, St. Louis, MO).

28,29 To assess the consequences of miR-155 inhibition, and the resulting decrease in NO production, on CD11b expression, we performed immunocytochemistry to evaluate CD11b labelling in N9 cells. For this purpose, N9 microglia cells were transfected with anti-miR-155 or control oligonucleotides 24 hr before exposure to LPS (0·1 μg/ml). Following 18 hr of incubation with LPS, cells were fixed and labelled with the nuclear dye DAPI, with a specific anti-CD11b antibody and an antibody against the structural protein tubulin (Fig. 7). Results in Fig. 7 clearly show that exposure to LPS STI571 research buy increases CD11b labelling in

N9 cells (Fig. 7e), with respect to control cells (Fig. 7a). In this regard, it was also possible to

observe striking differences in cell morphology, because LPS-treated cells lose the characteristic star Ruxolitinib chemical structure shape of resting N9 cells and become round and amoeboid, a common feature of activated microglia cells. Similar results were observed in N9 cells transfected with control oligonucleotides followed by LPS exposure (Fig. 7m). These cells present the same intense CD11b labelling and round shape of untransfected, LPS-treated cells. However, cells transfected with the anti-miR-155 oligonucleotides before LPS treatment showed less intense CD11b labelling and a morphology closer to that of control cells (Fig. 7i), indicating

lower levels of CD11b. In view of the pro-inflammatory Selleck Osimertinib role of miR-155 in activated microglia, as evidenced by our results on N9 cells, we evaluated the potential of miR-155 modulation as an anti-inflammatory and neuroprotective strategy. For this purpose, N9 microglia cells were transfected with anti-miR-155 or control oligonucleotides 24 hr before exposure to LPS (0·1 μg/ml). Following 18 hr of incubation with LPS, the medium of N9 cells was collected and mixed with Neurobasal medium at a ratio of 1 : 1 (v/v). Primary cultures of cortical neurons were incubated with this mixture (conditioned medium) for 24 hr before assessment of cell viability using the Alamar Blue assay (Fig. 8). In parallel, cortical cultures were exposed directly to the same concentration of LPS (0·1 μg/ml). Figure 8 shows that neurons exposed to conditioned medium collected from N9 cells, previously incubated with LPS in the absence of transfection, presented a reduction in viability of 40%. Similar results were observed in neurons incubated with conditioned medium collected from cells transfected with control oligonucleotides. However, neurons treated with medium conditioned by N9 cells, in which miR-155 had been inhibited before LPS treatment, presented only a slight decrease in viability (10%) with respect to control neuronal cells.

We find that LKB1 is required for several key metabolic processes in T-cell progenitors. For example, LKB1 controls expression of CD98, a key subunit of the L-system aa transporter and is also required for the pre-TCR to induce and sustain the regulated phosphorylation of the ribosomal S6 subunit, a key regulator of protein synthesis. In the absence of LKB1 TCR-β-selected thymocytes Proteasome cleavage failed to proliferate and did not survive. LBK1 was also required for survival and proliferation of peripheral T cells. These data thus reveal a conserved and essential role for LKB1 in the proliferative responses

of both thymocytes and mature T cells. “
“The mechanisms underlying Japanese encephalitis virus (JEV) pathogenesis need to be thoroughly explored to delineate therapeutic approaches. It is believed that JEV manipulates the innate and adaptive compartments of the host’s immune system to evade BMN 673 immune response and cross the blood–brain barrier. The present study was thus designed to investigate the functional modulation of DCs after exposure to JEV and to assess the consequences on CD4+ T-lymphocyte functions. Human monocyte-derived DCs were either infected with 1 MOI of live virus, UV-inactivated

virus, or were mock-infected. Replication-competent JEV induced a significant increase in the expression of maturation markers 48 h postinfection, along with that of programmed cell death 1 ligand 1 (PD-L1; also called B7-H1 and CD274). JEV-infected DCs expanded the Treg cells in allogenic mixed lymphocyte reactions. The expansion of Treg cells by JEV-infected DCs was

significantly reduced upon blocking PD-L1 using an antagonist. In addition, JEV-infected DCs significantly altered the proliferation and reduced the polarization of Th cells toward the Th1-cell phenotype. The results, for the first time, Tobramycin suggest that JEV evades the host’s immune system by modulating the crosstalk between DCs and T lymphocytes via the PD-L1 axis. “
“In this study, we elucidated the role of tumor necrosis factor (TNF)-α in the host defense to pulmonary infection with Streptococcus pneumoniae and defined the cellular source of this cytokine at an early stage of infection. Administration of anti-TNF-α monoclonal antibody (mAb) resulted in the reduced accumulation of neutrophils in bronchoalveolar lavage fluids (BALFs) and severe exacerbation of this infection. In a flow cytometric analysis, the intracellular expression of TNF-α was detected in Gr-1bright+ and Gr-1dull+ cells during the time intervals postinfection, and F4/80+ cells expressed intracellular TNF-α before Gr-1dull+ cells appeared. The Gr-1bright+ and Gr-1dull+ cells sorted from BALF cells at 24 h were identified as neutrophils and macrophage-like cells, respectively, and the Gr-1dull+ cells expressing CD11c, partially CD11b and a marginal level of F4/80 secreted TNF-α in in vitro cultures.

Since the 1980s, the main objective

of VL diagnostics development has been to replace the visual identification of parasites in tissue, a technique that is invasive and requires considerable expertise. Moreover, the use of whole parasite extracts in the serologic tests is limited because of the low reproducibility and low specificity values obtained. Several serological tests have been developed, but none of them are specific for VL, although they have proved to be useful in combination with a clinical case definition (20). So, to obtain a specific diagnosis for VL, some purified recombinant Leishmania antigens have been proposed (21). The present study describes the expression, isolation and purification of two recombinant proteins from L. chagasi, rLci2B and rLci1A that were previously selected from a cDNA library, followed by standardization of an ELISA using South America canine sera, to contribute selleck products to the diagnostic of dog’s infection provoked by the protozoa parasite. Both proteins were produced in Escherichia coli, and their sequences were registered by the National Institute of Industrial Property – Brazil (INPI) under paragraph PI0900961-2, with the title: ‘Use of antigens of Leishmania in methods for diagnosis, therapy and vaccine for leishmaniasis’. The rLci2B protein has homology with a parasite cytoskeleton protein kinesin, while rLci1A has homology with the heat shock protein 70 (HSP70). The

HSP70 family belongs to Rutecarpine a class of proteins highly conserved throughout evolution and has an immunogenic activity

(22). Antibodies to specific recombinant antigens such find more as heat shock protein 70 (rHSP70) and kinesin K39 (rK39) have also been shown to be good markers to detect infection (23). Thus, this study will be useful to expand the panel of recombinant antigens for the development of more sensitive and specific serodiagnostic tests for this disease. All reagents used were of analytical grade. Distilled water was filtered and deionized using a Millipore water purification system. The sera used in this study were collected from domestic dogs from three Brazilian regions: Northeast, Southeast and Midwest. The serum samples were collected by venipuncture by veterinaries of three research centres: Centro de Pesquisa Aggeu Magalhães, Pernambuco; Instituto de Pesquisa Evandro Chagas, Rio de Janeiro and Centro Gonçalo Muniz, Bahia, between 2006 and 2008. The sera were stored at −70°C and transferred to our laboratory. The panel of 56 negative sera used for determining the cut-off came from the state of Rio de Janeiro. The multicentre panel of 119 negative sera used in the assay came from the Southeast (79), Midwest (26) and Northeast (14) regions of Brazil. The multicentre panel of 138 positive sera used in the challenge originated in the Southeast (38), Midwest (46) and Northeast (54) regions of Brazil. The panel of 86 negative sera for L.

burgdorferi (Fikrig et al., 1991). Therefore, a major emphasis in B. burgdorferi research has been DNA Damage inhibitor to develop a new vaccine that could be used as a safe and effective second-generation preventative against Lyme disease. As B. burgdorferi is an extracellular pathogen, and humoral immunity has been shown to be protective

against this organism, vaccine studies have revolved around identifying borrelial antigens that are (1) surface exposed, (2) conserved among different strains and genospecies of Borrelia spirochetes, and (3) produced during tick transmission and mammalian infection. Any outer surface protein that fulfills these three basic requirements is considered an excellent candidate for vaccine studies. As the surface of B. burgdorferi is the interface between the host and pathogen during infection, outer membrane proteins (OMPs) also have been implicated as important virulence factors. As a first step in identifying borrelial proteins that are surface exposed, many laboratories performed microarray analyses

to examine the global response of gene expression in B. burgdorferi after exposure to either temperature shift or cultivation within a mammalian host environment (Revel et al., 2002; Brooks et al., 2003; Ojaimi et al., 2003; Tokarz et al., 2004). The underlying assumption in these studies, which has been supported by empirical data, is that genes upregulated by temperature will correspond to genes upregulated during tick feeding and transmission to the mammalian host, while genes upregulated during cultivation MG-132 in vivo science in a mammalian host correspond to genes upregulated during mammalian infection. Using these two different environmental stimuli, numerous

genes that are upregulated during tick feeding and/or mammalian infection were identified. Among the genes observed to be upregulated by temperature- and/or mammalian-specific signals, over 50 have been shown to encode known or putative leader peptides, indicating that they may encode outer surface proteins (Revel et al., 2002; Brooks et al., 2003; Ojaimi et al., 2003; Tokarz et al., 2004). Further, many of the genes identified were observed to encode hypothetical OMPs that had not previously been characterized. Therefore, a major goal in the Lyme disease field in recent years has been to further characterize surface-exposed proteins by (1) determining their cellular location throughout the enzootic cycle of B. burgdorferi, (2) examining their overall conservation among different strains and genospecies of B. burgdorferi, and (3) assessing their ability to protect mice and nonhuman primates from experimental Lyme disease. The combined studies have led to the identification of several candidate vaccine molecules and to the identification of many virulence determinants. The enzootic life cycle of B. burgdorferi is complex and typically involves horizontal transmission between ticks of the genus Ixodes and wild rodents (Lane et al., 1991).

Transactivation of human HLA-I (HLA-A, -B, -C, -E, -F, -G) and TAP1 genes was measured by a dual luciferase assay. For this purpose, we used previously described reporter plasmids [47] encoding the firefly luciferase Selumetinib in vivo gene under control of the respective promoter elements. A549 cells were transfected with reporter plasmids (2 μg) and constitutively active

renilla luciferase vector (200 ng) as transfection control in a 24-well plate. At 24 h after transfection, cells were left uninfected or infected with HTNV (MOI = 1.5) for 1 h at 37°C. Normal culture medium was added to cells and cultures were incubated for 4 days. As a positive control, IFN-α-treated cells were used in all assays unless otherwise specified. Next cells were lysed with passive lysis buffer (Promega) for 15 min at room temperature with gentle agitation. Subsequently, reporter activity was measured by Dual-Luciferase Assay System (Promega) and a Mithras LB96V luminometer (Berthold). LightCycler qRT-PCR was performed essentially as previously described [46]. Briefly, cells were lysed with MagNA Pure lysis buffer (Roche) and mRNA was isolated with a MagNA Pure-LC device using standard protocols.

RNA was reverse-transcribed this website with Avian myeloblastosis virus reverse transcriptase and oligo (dT) primer using the First Strand cDNA Synthesis Kit from Roche. For amplification of target sequences, LightCycler Primer Sets (Search-LC) were used with LightCycler FastStart DNA Sybr Green I Kit (Roche). RNA input was normalized by the average expression DNA ligase of the housekeeping genes encoding β-actin and cyclophilin B. By plotting a known input concentration of a plasmid to the PCR cycle number at which the detected fluorescence intensity reached a fixed value, a virtual standard curve was generated. This standard curve was used to calculate transcript copy numbers. The presented relative copy numbers are mean averages of data of two independent analyses for each sample and parameter. A549 cells or Vero

E6 cells treated with IFN-α (ImmunoTools) or IFN-λ1 (R&D) for 8 h were used as a positive control. Vero E6 cells were left uninfected or infected with HTNV (MOI = 1) for 4 days or infected with VSV (MOI = 1) for 8 h. Subsequently, RNA was extracted from infected cells by using TRIzol (Sigma) following the manufacturer’s instructions. RNA was quantified by using a NanoDrop 2000 spectrophotometer (Thermo Scientific Inc.). The RNA (1 μg/well) was reverse transfected into Vero E6 cells in a 48-well plate by using lipofectamin 2000 (Invitrogen) following the manufacturer’s instructions. Vero E6 cells were harvested 24 h after transfection and analyzed by FACS for MHC-I surface expression. For blocking innate signaling through the TBK1/IKK3 signaling axis, the chemical inhibitor BX795 (InvivoGen) was used.

The MCV (mean corpuscular volume, volume per individual erythrocyte) was also reduced in these mice, confirming the successful induction of IDA characterized by microcytic anemia. Iron-deficient mice were infected with Plasmodium yoelii (Py) and the kinetics of infection assessed by evaluating the daily levels of parasitemia and survival rates.

Py has two substrains, PyL and PyNL, each with differing virulence. Infection of iron-sufficient mice with the virulent strain, PyL, resulted in a rapid increase in parasitemia that killed all mice within 10 days (Fig. 1A). Interestingly, IDA mice showed markedly lower levels of parasitemia throughout the period of infection and survived longer than iron-sufficient find more control mice. They finally succumbed to infection with low levels of parasitemia, presumably due to severe anemia (Fig. 1A). Mice infected with LD50 of the PyNL strain (less virulent than PyL) experienced peak levels of parasitemia 3 wk after infection followed by complete eradication of the parasites. Mice cured of PyNL infection showed sterile immunity against otherwise-lethal infections by PyL 8. IDA mice had low levels of parasitemia and all of them survived (Fig. 1B). A detailed evaluation showed that the numbers of late trophozoites and shizonts were

significantly reduced (Fig. 1C). These results clearly demonstrated that IDA mice were protected from death caused by acute Py infection. This protection was Interleukin-2 receptor not limited to infection with Py, as similar results were obtained when IDA mice were infected with the P. berghei NK65 strain (data not shown). To address MK-1775 price the mechanisms underlying resistance to malaria in IDA, two possibilities were raised. One relates to the direct effects

on the parasites themselves; the development/growth of the parasites is suppressed in IDA erythrocytes. The other is that iron-deficiency modulates host immunity to enhance the eradication of parasites. We first focused on the intra-erythrocytic development of the malaria parasites. Erythrocytes isolated from IDA mice during the early phase of PyL infection were cultured in the presence of 10% normal mouse serum and periodically observed under a microscope. The purified infected cells were almost ring-infected and developed into late trophozoites within 3 h. They developed into mature schizonts after nuclear division within 6 h. PyL parasites grew equally well in IDA erythrocytes and control erythrocytes (Fig. 2A). To further mimic the in vivo situation, we used serum from IDA mice. Under these conditions the parasites still grew in the presence of IDA serum (Fig. 2A). Furthermore, we did not observe any differences in the number of merozoites within the individual mature schizonts in vivo (Fig. 2B). These results seem to exclude the possibility that IDA adversely affects the development/growth of malaria parasites. We next analyzed the effects of IDA on host immunity.

Although it is unclear why the MicroScan results for clindamycin were often above the range within ± 2 log2 dilutions as revealed by the reference method, it may be associated with clindamycin acting bacteriostatically and the

MicroScan panel being read visually. Bacillus cereus BSIs were reported to be found in immunosuppressed patients, patients receiving continuous intravenous therapy, patients with underlying malignancy, and neonates (Drobniewski, 1993; Gaur et al., 2001). In this study, use of antimicrobials for more than 3 days during the 3-month period before isolation of B. cereus was significantly larger in the BSI group compared with the Selleck LY2157299 contaminated blood culture group. In conclusion, our results suggest that the virulence gene profiles may be indistinguishable between BSI isolates and isolates from contaminated

blood cultures. In each group, there was wide diversity in the patterns of the virulence genes examined. Compared with the reference MICs, some isolates showed discrepant MIC values determined by the MicroScan or the Etest method for some antimicrobials. We consider that antimicrobial susceptibility data are essential when selecting the treatment regimen for B. cereus infections, because of the existence of isolates showing higher MICs for antimicrobials such as β-lactams and quinolones as shown in this study. Therefore, it is important to characterize the clinical utility and the performance limitations of antimicrobial susceptibility testing methods routinely used for Trametinib price clinical B. cereus isolates. Our results also suggest that Tacrolimus (FK506) prior antimicrobial therapy may be a risk factor for BSIs due to B. cereus. To prevent BSIs caused

by B. cereus, therefore, clinicians should make efforts to improve the quality of antimicrobial therapy. T.H. was partially supported by a Grant-in-Aid for Scientific Research (20790413) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. No conflict of interest to declare. “
“Enteropathogenic Escherichia coli (EPEC) strains produce a bundle-forming pilus (BFP) that mediates localized adherence (LA) to intestinal epithelial cells. The major structural subunit of the BFP is bundlin, which is encoded by the bfpA gene located on a large EAF plasmid. The perA gene has been shown to activate genes within the bfp operon. We analyzed perA gene polymorphism among typical (eae- and bfpA- positive) EPEC strains isolated from healthy and diarrheal persons in Japan (n= 27) and Thailand (n= 26) during the period 1995 to 2007 and compared this with virulence and phenotypic characteristics. Eight genotypes of perA were identified by heteroduplex mobility assay (HMA). The strains isolated in Thailand showed strong autoaggregation and had an intact perA, while most of those isolated in Japan showed weak or no autoaggregation, and had a truncated perA due to frameshift mutation.

Consideration of these factors when enrolling subjects and controlling for them in analyses will minimize erroneous interpretation of results in the continuing battle against HIV. Time preparing this manuscript was supported by 1K23HD062340-01 (Anderson-PI) and K24 AI066884 (Cu-Uvin-PI). “
“Ectoenzymes are a diverse group of membrane proteins that have their catalytic sites outside the plasma membrane. Many of them are selleck products found on leukocytes and endothelial cells, and they

are multifunctional in nature. Collectively, different ectoenzymes can modulate each step of leukocyte–endothelial contacts, as well as subsequent cell migration in tissues. Here, we review how ectoenzymes belonging to Selleckchem Vemurafenib the oxidase, NAD-metabolizing enzyme, nucleotidase and peptidase/protease families regulate and fine-tune leukocyte trafficking, and how ectoenzymes have been targeted both in preclinical and clinical trials. Leukocyte traffic is governed by the canonical multistep extravasation cascade 1. Selectins, chemokines and integrins, and their counter-receptors, have firmly established roles in controlling

rolling, activation, firm adhesion and transmigration of different types of leukocytes within the blood vessels (Fig. 1). However, each step of the cascade is modified by various other molecules under physiologic and pathologic conditions. Ectoenzymes are a unique class of cell-surface-expressed enzymes 2. Since their catalytic domains face outside the cell membrane, they are fundamentally different from both the multitude of intracellular signaling molecules and the cell-surface-expressed enzymes with cytoplasmic catalytic domains (e.g. G-proteins (receptor) kinases, phosphatases and down-stream signaling molecules), which are also critical in leukocyte migration. Apart from the extracellular catalytic

activity that is common to all, ectoenzymes are a diverse class of molecules that are involved in very different types of enzymatic reactions MRIP (Fig. 2). However, a common theme in ectoenzymatic regulation of leukocyte traffic is that often both the substrate(s) and the end-product(s) can modulate leukocyte migration 3. Here, we will mainly focus on selective examples of ectoenzymes from different classes, including CD26, CD38, CD39, CD73, CD156b, CD156c, CD157, CD203 and the primary amine oxidases, which are the best characterized in terms of leukocyte trafficking. We will emphasize the models based on gene-deficient mice and the potential applicability of ectoenzymes in alleviating inappropriate inflammation. We will focus on the general concepts and advances that have been published since our last comprehensive review on this topic in 2005 3.