No wound complications occurred, and all patients could resume oral intake. The cephalic vein is a more reliable recipient vein than is the internal mammary vein. The skin graft-covered pectoralis major muscle flap provides secure external coverage to prevent anastomotic leakage

even in complicated cases. Combined use of the cephalic vein and the skin graft-covered pectoralis major muscle flap is a versatile option for secondary thoracic esophageal reconstruction. © 2013 Wiley Periodicals, Inc. Microsurgery 34:319–323, 2014. “
“Treatment of recurrent carpal tunnel syndrome (CTS) is challenging, selleck products especially in a case with recurrent CTS and a neuroma formation. Resection of the neuroma causing the syndrome, reconstruction of the nerve gap of the median nerve, and covering up the reconstructed median nerve with well-vascularized soft tissue for prevention of CTS re-recurrence are the essential RAD001 supplier procedures. We report a case of recurrent CTS with severe pain due to a neuroma-in-continuity successfully treated using a free anterolateral thigh (ALT) flap with a vascularized lateral femoral cutaneous nerve (LFCN). A 2 cm neuroma existed in the median nerve and was resected.

The nerve gap was repaired using a vascularized LFCN included in the ALT flap. The ALT flap was transferred to the wrist to cover the median nerve. The severe pain disappeared completely and the sensory and motor impairment of the median nerve improved 5 months after the free flap surgery, as the Tinel’s sign

moved distally away from the wrist and disappeared. The result of the Semmes-Weinstein test improved from 5.08 to 4.31 and she was able to flex and extend the right wrist and fingers without pain. CTS did not recur 15 months after the surgery. A free ALT flap with vascularized LFCN allows nerve reconstruction for the median nerve gap created after neuroma resection and coverage of the median nerve with well-vascularized soft tissue to prevent adhesion and CTS recurrence. © 2013 Wiley Periodicals, Inc. Microsurgery 34:145–148, 2014. “
“This report describes two incidental findings of aberrant Sunitinib branches of the radial digital nerves in the middle finger of a 52-year-old man who cut himself with a grinding machine, and in the index finger of a 45-year-old female who sustained a flexor sheath infection following a dog bite. In both patients, two equally sized radial digital nerves were found and both nerves originated from one common digital nerve. © 2010 Wiley-Liss, Inc. Microsurgery, 2010. “
“Although increasingly rare, failed microsurgical flaps are a complicated clinical problem when they occur. Review of reports of management following microsurgical flap failure offers an outline of options. A substantial number of breast and extremity patients elect abandonment of reconstruction. The majority of head and neck, breast, and extremity patients proceed to nonmicrosurgical reconstructive options.

To this end, we used a transgenic ERE-luciferase (Luc) reporter mouse model [13]. One recent 10-week Phase II clinical trial investigated an agonist of ERα (Org 37663) in postmenopausal RA, and found no clinical benefit despite induction of oestrogenic responses in several organ systems [14]. In another recent

12-week Phase II trial an agonist of ERβ (ERB-041) was investigated, and similar results were found [15]. One explanation may be that the duration of the trials was not long enough to induce clinical benefit, as a previous trial with HRT showed benefit only after 2 years. As animal studies with both compounds had shown anti-arthritic properties, it is important to investigate PLX4032 cost further the mechanisms for these effects, and to evaluate whether there is a difference between different species [16,17]. Indeed, we have shown previously that stimulation of ERα ameliorated CIA in mice, whereas an agonist of ERβ did not, while the specific ERβ agonist ERB-041 improved arthritis in rats [18]. Based on the current study, we conclude that neither the SERM raloxifene nor oestradiol had any effect on the induction phase of CIA. Oestradiol, but not raloxifene, modified the effector phase of the disease in CAIA. Raloxifene activated the OSI-906 mouse classical signalling pathway to promote gene transcription, although not to the same extent as oestradiol. However, both compounds displayed potent anti-osteoporotic properties in lipopolysaccharide (LPS)-induced bone

loss seen in CAIA. The ethical committee for animal experiments at Gothenburg University approved this study. Female DBA/1 mice were purchased from Taconic M&B A/S (Ry, Denmark). Male transgenic 3 × ERE-TAT-Luc (ERE-luciferase) mice, on a mixed CBA × C56Bl/6 J background, were generated as described previously [13]. Mice were electronically tagged and kept, five to 10 animals per cage, under standard environmental conditions, and fed standard laboratory chow and tap water ad libitum. OVX and sham operations were performed at 10 weeks of age. Ovaries were removed through a midline incision of the skin, and flank incisions of the peritoneum. The skin incision was then closed with metallic clips. Sham-operated

animals had their ovaries exposed but not removed. Orchiectomy was performed at 20 weeks of age. Testes were removed through an incision of the scrotum, and the incision Etofibrate was closed with a metallic clip. Surgery was performed after ketamine (PfizerAB, Täby, Sweden) and medetomidin (OrionPharma, Espoo, Finland) anaesthesia. Carprofen (OrionPharma) was used postoperatively as a painkiller. Induction phase.  CIA was induced 2 weeks after OVX in female DBA/1 mice. Treatment with raloxifene, oestradiol or vehicle 5 days per week was started 2 days prior to immunization and continued for 12 days. A booster injection of collagen II with incomplete Freund’s adjuvant was given 3 weeks after immunization, and arthritic score and severity were monitored. Mice were terminated 2 weeks later. Effector phase.

Therefore the events that govern early B-cell activation following influenza virus infection are crucial for ameliorating disease outcome. The mechanisms underlying early B-cell activation, however, are incompletely understood. Rapid Ab

production originates from extrafollicular foci developing at the edges of the T- and B-cell zones in secondary lymphoid tissues following antigen exposure. These responses are thought to generate primarily short-lived plasma cells 9. Rapid Ab production at extrafollicular sites is attributed to T cell-independent as well as T-dependent responses 10, 11. Rapamycin research buy In contrast, the slower intrafollicular germinal center reactions require cognate CD4 T-cell–B-cell interactions 12, 13. They are regarded as the birthplace of long-lived humoral immunity, providing both memory B cells and long-lived plasma cells 11, 13. Both extra and intra-follicular responses develop strongly in the regional

LN following selleck chemicals influenza virus infection 14. The selection events that underlie the establishment of extrafollicular versus germinal center B-cell responses are important events in the initiation of the adaptive immune response. They coordinate the formation of crucial rapidly protective responses, while ensuring long-term protection from re-infection 11. There is evidence that rapid (antiviral) Ab production can be provided by distinct B-cell subsets 1, 11, 15–19. Marginal zone (MZ) B cells are one such subset. They can respond to blood-borne antigens through rapid production of Ab at extrafollicular sites 17, 18. In the mouse these B cells are only found in the spleen, however, and not in LN 20, 21. Thus, MZ B cells are unlikely to play a role in the response to influenza virus infections, as respiratory tract draining MedLN are the main sites of the initial influenza virus-induced B-cell response 14. Whether there are other subsets in the LN that act as functional equivalents to splenic MZ B cells is currently unknown. Recently, BCR affinity-guided selection events have been implicated as a factor that could determine the B-cell fate following protein immunization 22. Paus et al.22 used an elegant

adoptive cell transfer approach with transgenic hen egg lysozyme-specific B cells to provide evidence that BCR affinity thresholds exist that steer B cells toward CYTH4 a particular response. In that study high-affinity B cell–antigen interactions resulted in predominantly extrafollicular foci responses, whereas hen egg lysozyme-specific B cells binding antigen with weaker overall affinities were predominately selected into the germinal center response. These data are consistent with a study on vesicular stomatitis virus infection-induced B-cell responses, in which Roost et al. observed no improvement on the overall Ab-affinity during the course of vesicular stomatitis virus infection and showed that early induced virus-specific Ab are of relatively high affinities 23.

Our observation that the CD8α− DCs were mostly inefficient to induce protective CD8+ T-cell memory may indeed result from an intrinsically low ability to activate naïve CD8+ T cells and/or to efficiently reach the T-cell area of the spleens after the transfer. An alternative explanation may be that only very few CD8α− cDCs are infected in vivo, which prevent them from efficiently inducing CD8+ T-cell memory. In that latter scenario CD8α− cDCs would still intrinsically be able to prime protective

CD8+ T-cell memory, although this mechanism would only be of minor contribution. Selleck Apoptosis Compound Library Whatever the true explanation is, our report supports a crucial role of CD8α+ cDCs cells for most potent induction of CD8+ T-cell memory. Recent studies have shown SB431542 mouse a role

of CD11c+ cells, and in particular CD8α+ cDCs, in the transport of live Lm from the marginal zones to the splenic white pulps, suggesting that the primary function of these cells may be to uptake pathogens to the organs of infected animals, even before the priming of T cells 8, 21, 31. However, others 22, 32 suggested that marginal zone macrophages, but not CD8α+ cDCs, are taking up particulate antigens as well as dead bacteria Verteporfin (Lm, E. coli and S. aureus) from the blood. Here and in agreement with a previous study

33, we reconcile these discrepancies by showing that (i) the great majority of spleen cells staining positive for Lm antigens (i.e. containing live, dead Lm or soluble Lm antigens) are phagocytes (macrophages, neutrophils and monocytes) that also express antimicrobial effector functions and (ii) CD8α+ cDCs, which are specialized APCs, represent the main subset of live bacteria-containing cells. Even though our experiments used the secA2− mutant of Lm, our results are in line with those from other laboratories that used wt Lm. We had also previously shown that the early distribution of live (GFP+) secA2−Lm matched that of wt and actA−Lm16, collectively suggesting that this experimental system may help us unravel the mechanisms of protective immunization. Therefore, our results support the idea that phagocytes rapidly capture and kill the majority of blood-injected bacteria whereas CD8α+ cDC provide a replicative niche, thus representing the most actively infected cell type in vivo. In such context, it is tempting to speculate that only direct priming and not cross-priming is inducing fully competent and protective memory CD8+ T cells, a still ongoing controversy in the field 34–36.

We have shown that DX5+CD4+ T cells can have suppressive effects on CD8+ T cells and can change the outcome of CD4+ T-cell responses in vitro [24, 25]. Upon antigen-specific RAD001 nmr triggering of naïve OVA-specific CD4+ T cells in the presence of DX5+CD4+ T cells, a striking difference in cytokine production was observed. An IL-10-producing CD4+ T-cell response was induced instead of the predominant IFN-γ-producing Th1 reactions normally seen in mice on a C57BL/6 background. This modulation did not require cell–cell contact. Instead, IL-4 produced by DX5+CD4+ T cells

was primarily responsible for the inhibition of IFN-γ and promotion of IL-10 production by responding CD4+ T cells. These data therefore indicate that DX5+CD4+ T cells can directly modulate the outcome of Th responses by diverting potentially

pathogenic Th1 induction into Th responses characterized by the production of IL-10. The studies described above demonstrate that DX5+CD4+ T cells can modulate the outcome of Th responses by directly acting on the responding CD4+ T cells but do not exclude the possibility that DX5+CD4+ T cells also have an impact on DCs. Modulation of DCs could represent another strategy by which DX5+CD4+ T cells influence the outcome of immune responses. DCs are professional APCs that play a major role in determining whether proinflammatory or regulatory Th cells are induced [23]. Depending on SCH727965 chemical structure the type of pathogen they encounter, DCs are able to direct the development of naïve CD4+ T cells to several distinct Th cell subsets. For example, IL-12 produced by DCs after TLR-4 triggering biases the CD4+ T-cell response toward the differentiation of a Th1 response that is characterized by the production of IFN-γ [26-28]. Co-stimulatory molecules expressed on DCs are also playing a central role in maintaining the balance between immunity and tolerance. Molecules, such as CD80 and CD86, can promote T-cell activation [29, 30], whereas molecules such as programmed death ligand-1 (PDL-1, B7-H1) and PDL-2 (B7-DC) can inhibit T-cell responses [31-33]. The latter molecules are therefore instrumental in the

induction of T-cell tolerance and prevention of auto-immunity [34-37]. The interaction between programmed death (PD) ligands and their receptor PD-1 is involved in T-cell exhaustion and failure of viral control see more during chronic infection [38]. This pathway is also involved in the attenuation of protective immune response against tumors [39-41] and has been shown to regulate the development, maintenance, and function of Treg cells. In this study, we have analyzed the potency of the DX5+CD4+ T-cell population to modulate DC function. Our results indicate that DX5+CD4+ T cells can inhibit the production of IL-12 by DCs resulting in the inhibition of Th1-cell responses. These results therefore add to our understanding of the immunomodulatory potential of DX5+CD4+ T cells.

Lack of the glomerular expression of CD2AP in animals produces heavy proteinuria. This is the first study of CD2AP gene in

SRNS patients from Indonesia. Objectives: To identify and analyse mutations on CD2AP gene in steroid resistant LDE225 supplier Nephrotic Syndrome patients from Indonesia. Methods: DNA was extracted from peripheral blood leukocyte, using a salting-out method, primer delineated, amplification of the CD2AP exons was performed by PCR (in 18 exons), electrophoresis of PCR product were using Gel Agarose 1%, then followed with DNA sequencing and interpretation of DNA sequencing. Results: This study involved 18 subject, male 11 (61.1%), female 7 (38,9%) with age range 4–23 years. A renal biopsy was performed in 8 patients and showed focal segmental glomerulosclerosis (FSGS) in 5 patients, minimal changes nephrotic syndrome (MNCS) in 3 patients. Mutations and polymorphisms analysis of CD2AP by direct exon sequencing was performed in all 18 patients. We found 4 SNPs (single nucleotide polymorphisms) from 18 exons of CD2AP. The SNPs were in exon 4 (c.320-113 C > T), exon 11 (c. 1108 + 82 T > C), exon 16 (c.1814 + 24 G > A), exon 18 (c.1879-66 T > C). There were no mutations of CD2AP from our patients. Conclusion: From this study only found SNPs

and did not found any mutations. Further studies needed in different genes. KURIBAYASHI-OKUMA EMIKO1, HISAKI HARUMI2, OKAZAKI TOMOKI2, UCHIDA SHUNYA1 1Department of Internal Medicine, Teikyo University School of Medicine; 2Department of Biochemistry, Teikyo University School of Medicine Introduction: Steroid-resistant AT9283 order nephrotic syndrome is intractable kidney disorder often associated with the progression to end stage renal disease. To treat steroid-resitant nephrotic syndrome, LDL-apheresis (LDL-A) has been instituted and its efficacy is reported to be about

50%. In the present study Protein kinase N1 the mechanism whereby LDL-A does or does not induce the remission of steroid-resitant nephrotic syndrome was investigated using the proteomic analysis of the plasma proteins adsorbed from the patients. Methods: The effect of LDL-A was assessed by the clinical indicators such as proteinuria and serum albumin. The patients were grouped as responder (n = 4) and non-responder (n = 4). The adsorbed plasma proteins were obtained at the first and the last sessions of the apheresis. Following the removal of albumin and gamma-globulin, the samples were separated by two-dimensional differential in-gel electrophoretic analysis (2-D DIGE). All spots were picked and subjected for in-gel digestion with trypsin followed by peptide analysis by MALDI-TOF/MS. Results: Since 2D patterns of the adsorbed proteins in non-responder group were almost identical between the first and the last sessions of the apheresis, we focused on the difference of 2D patterns in the first and the last sessions in responder group.

Infected red blood cells from the blood of infected mice (parasitemia, 30–50%) were purified (> 95%) by centrifugation in 74% Percoll density gradient as described previously [21]. MHC II+CD11chiCD3−CD19−, MHC

II+CD11c−CD3−CD19−IgM+, and MHC II+CD11c−CD3−CD19−IgM− cells were purified by Everolimus cell line cell sorting as described. Cells (1 × 105) were cultured in the presence of iRBC or RBC (4 × 106) in a final volume of 200 µL for 16 hr and the concentrations of cytokines in the supernatant determined by a sandwich ELISA as described previously [22]. OT-II mice were immunized i.p. with OVA (200 µg) in complete Freund’s adjuvant. After 5 days, CD4+ T cells were prepared from the spleens of OT-II mice using a CD4+ T cell isolation kit (Milteny Biotech, CD4+ T cells; 87.5%) and labeled with 15 µM CFSE (Invitrogen, Carlsbad, CA, USA) for 10 min. MHC II+CD11chiCD3−CD19− DCs and MHC II+CD11c−CD3−CD19− cells were prepared by cell sorting and pulsed with OVA323–339 (10 µg/mL) or with OVA (1 mg/mL) for 3 hr. OT-II (1 × 105) and MHC II+CD3−CD19− cells (1 × 104) were cocultured for 3 days and cell divisions assessed on the basis of diminution of CFSE dye using a FACS Canto II. The supernatant was collected after 2 days of culture to measure the concentrations of IL-2. ELISA was performed as described previously [22]. The statistical significance

of differences was determined by two-sided Student’s t-test using Wnt inhibitor GraphPad PRISM 5 software. P values less than 0.05 were considered significant. After excluding T and B cells with CD3 and CD19 markers, MHC class II+ cells were examined using spleen cells from B6 mice infected with P. yoelii. Splenic CD3−CD19− cells were Y-27632 research buy stained for CD11c and MHC II, and MHC II+ cells divided into three subpopulations based on the degree of CD11c expression, namely CD11chi, CD11cint and CD11c− cells (Fig. 1a). In MHC II+CD3−CD19− cells, the degree of MHC II expression was greater in CD11chi cells (MFI: uninfected, 6199; infection day 8, 3279) than in CD11cint (MFI: uninfected, 2884; day 8, 2219) or CD11c− (MFI: uninfected, 2638; day 8, 1295) cells.

MHC II+CD11chiCD3−CD19− cells included conventional DCs and constituted the major population of MHC II+ cells prior to infection. MHC II+CD11cintCD3−CD19− cells included plasmacytoid DCs and regulatory DCs [7]. After day 5 post-infection, the numbers of both MHC II+CD11chiCD3−CD19− and MHC II+CD11cintCD3−CD19− cells decreased steadily (Fig. 1b). In contrast, the number of MHC II+CD11c−CD3−CD19− cells increased until day 9 post-infection in parallel with the degree of parasitemia (Fig. 1c). However, the number of these cells decreased after day 11 post-infection despite continuing increase in parasitemia. These MHC II+CD11c−CD3−CD19− cells were next stained for CD138, a plasma cell marker, and Igs (Fig. 2a).

The amount of phosphorylated p38, ERK 1/2 or STAT5 was calculated as stimulation index equal to the median fluorescence intensity (MFI)stimulated cells/MFIunstimulated cells.[16] Acquisition was performed using an LSR II flow cytometer (BD Bioscience); 5 × 103 events were

collected for analysis. To enumerate CD34+ cells, we used an established multiparameter gating strategy as previously described.[12] Methylcellulose colony assays were completed as previously described[12] using enriched CB CD34+ cells Selleckchem CP673451 at a plating concentration of 2 × 104 cells/35 mm × 10 mm culture dish (Falcon Plastics) in duplicate. Duplicate cultures were also grown in the presence of supernatant (1/10 final dilution in culture) for 14 days (5% CO2, 37°C). The role of GM-CSF and IL-5 in

supernatant stimulated Eo/B CFU formation was confirmed by adding 5 μg/ml anti-GM-CSF or anti–IL-5 (Peprotech, Rocky Hill, NJ) monoclonal antibodies to the supernatant-stimulated methylcellulose cultures. Eo/B colonies were defined as tight, round refractile cell aggregates of 40 cells or more, staining pink with eosin using Wright–Giemsa (Diff-Quik; Seimens, Newark, DE) and visualized by inverted light microscopy (Olympus CK 40, Olympus Co. Ltd, Tokyo, Japan).[17] Freshly isolated CD34+ progenitor cells were cultured in RPMI complete medium Dinaciclib datasheet in the absence or presence of LPS overnight. After overnight incubation

(37°C, Miconazole 5% CO2), the cell-free supernatant was harvested and stored at − 80°C for subsequent analysis. Multi-analyte profiling was performed and acquired using a Perkin Elmer CS 1000 Autoplex Analyzer (Luminex XMAP Technology; Austin, TX). A bioplex cytokine assay was used that simultaneously measured the concentrations of GM-CSF and IL-5 in culture supernatant using a human cytokine/chemokine MILLIPLEX MAP kit (Millipore, Mississauga, ON, Canada). The assay sensitivities of these cytokines were 2·3 and 0·1 pg/ml respectively. All analyses were performed according to the manufacturer’s instructions. To determine the mechanism of GM-CSF secretion, CD34+ cells were stimulated with 50 μm STAT5 inhibitor[18] or 50 μm PD98059[19] (ERK 1/2 inhibitor), or 20 μm SB203580[5] (p38 MAPK inhibitor) (Calbiochem, Cambridge, MA) or DMSO vehicle control for 45 min before LPS was added for overnight stimulation to induce GM-CSF secretion. These concentrations were found to be non-toxic to cells and of optimal dosage as determined by preliminary experiments. Data were analysed using IBM SPSS Statistics version 20·0 (Chicago, IL) and presented in figures as mean ± SEM.

Sample volumes were adjusted to patients’ body weight with a maximum for all samples combined of 10% of circulating volume. Because only limited amount of blood volume was often obtainable from the young patients, not all assays could be performed on all 25 patients. Mononuclear cells were isolated from heparinized blood samples (T1, T4 and T5) using the Ficoll Isopaque density gradient centrifugation (Amersham Pharmacia Selleck Decitabine Biotech, Uppsala, Sweden). Peripheral blood mononuclear cells were washed in FACS buffer (PBS containing 2% FCS and 0.1% sodium azide),

adjusted to 4.0×106 cells/mL in FACS buffer and blocked with normal mouse serum. The cells were incubated in 50 μL FACS buffer containing the appropriately diluted Fitc, PE, PercP or APC-labeled antibodies against human CD3, CD4, CD25, CD69, CD127, or GITR. For cytoplasmatic staining of cytotoxic T lymphocyte antigen 4 (CTLA-4) and Ki-67, the cells were first

surface stained, then fixed in Cytofix/Cytoperm (20 min, 4°C) and washed twice in Perm/Wash solution (Cytofix/perm kit, BD Biosciences, San Jose, CA, USA), followed by incubation with the appropriate antibody. Intranuclear staining of FOXP3 was performed after fixation and permeabilization according to the manufacturer’s protocol and subsequently incubated with the appropriate antibody. Antibodies against CD4 (clone SK3), CD25 (2A3), CD69 (L78), CD127 (hIL-7R-M21) and CTLA-4 (BN13) were obtained AZD6244 from BD Bioscience, GITR (110416) from R&D (Minneapolis, MN, USA) and Ki67 (MIB-1) from Immunotech (Marseilles, France), FOXP3 (PCH101) from eBioscience (San Diego, CA, USA). Finally,

stained mononuclear cells were washed twice in FACS buffer and run on a FACS Calibur (BD Biosciences). CellQuestPro software (BD Biosciences) was used for analyses. The gates for the different populations were set for the sample prior to surgery and kept identical for the following samples (Supporting Information Fig. 1A). From plasma obtained at five time points (immediately before and after surgery, and 4, 24 and 48 h after surgery), IL-6 and IL-8 levels were determined by multiplex STK38 immunoassay as previously described 47, 48. According to the intensity of CD25 expression, CD4+CD25bright, CD4+CD25intermediate and CD4+CD25 T cells were isolated from samples before surgery and 24 h after surgery. The gates for these three populations were kept identical at both time points. Isolation of total RNA and quantification of FOXP3 mRNA were performed as previously described 11. Forty million isolated peripheral blood mononuclear cells were stained for CD4 and CD25 as described above. Cells were fixated and stained for FOXP3 Alexa-488 (PCH101) according to manufacturer’s instructions (eBioscience). The cell sample was sorted by FACS in the three appropriate populations according to the intensity of CD25 expression.

They found that in both cases the receptor/ligand interaction resulted in enhancement of mast cell activation. Moreover, it was found that Staphylococcus aureus employs CD48, together with TLR-2, to invade CBMC and to activate

the production of pro-inflammatory cytokines 12. By identifying novel receptors on mast cells, Dr. Levi-Schaffer and colleagues hope to find new “self” regulating pathways and novel functions of mast cells in different patho-physiological settings 13. Leukotrienes (LT), histamine and proteases are among the major bioactive products of mast cells. Joshua Boyce (Boston, MA) reviewed data from his laboratory on the cysteinyl (cys) leukotrienes LTC4, LTD4, and LTE4 which are known to regulate mast cell function. Cys-LT are peptide-conjugated selleck chemicals lipid inflammatory mediators generated by mast cells, macrophages, basophils and eosinophils when these cells are activated in both innate and adaptive immune responses. They facilitate vascular leakage, smooth muscle constriction and cell migration. Nucleotides are released with cell injury, hypoxic stress, and with activation of macrophages and mast cells, mTOR inhibitor reaching high micromolar range concentrations in extracellular fluids. Both cys-LT and nucleotides are prominent and early mediators of inflammatory responses. The G protein-coupled

receptors for cys-LTs (Cys-LT1R and Cys-LT2R) are structural homologs of the G protein-coupled receptors for nucleotides, termed purinergic (P2Y) receptors. Dr. Boyce and colleagues demonstrated that both mouse and human mast cells express Cys-LT1R and Cys-LT2R, as well as multiple P2Y receptors for both adenine (P2Y1, P2Y2, P2Y12, P2Y13) oxyclozanide and uracil (P2Y6)-containing nucleotides 14. They have used mast cells as a model system to demonstrate both functional and physical interactions between these receptor classes that regulate cell proliferation, survival and mediator generation 15. Complementarity between

cys-LT receptors and P2Y receptors may be part of the innate danger-sensing repertoire of mast cells. Mast cells produce histamine, which is now recognized as also being made by a variety of other types of cells. The functions of histamine production from these cells remain unknown. However, only mast cells and basophils make and store significant amounts of histamine which is recognized by four different receptors (H1R-H4R) with tissue-specific expression patterns on immune and nonimmune cells and unique signaling pathways 16. As discussed by Paul Bryce (Chicago, IL), H4R is the most recently identified member of the histamine receptor family. Three potential isoforms of H4R have been described so far, including one activating receptor and two smaller putative dominant negative receptors. The importance of mast cell-produced histamine for DC function is only just beginning to be understood.