The efficacy of phagocytosis was determined by FACS analysis as described previously.23 Non-infected human neutrophils (3·75 × 106 cells) and monocytes (3 × 106 cells) were treated with PAR2-cAP and/or IFN-γ for 20 or 28 hr. Cell RG7204 nmr culture supernatants were collected and used for MCP-1 ELISA. Concentration of MCP-1 in the cell culture supernatants was measured with a human CCL2/MCP-1 (R&D Systems, Wiesbaden-Nordenstadt, Germany) ELISA kit according to the manufacturer’s instructions. Specific inhibitors of intracellular signalling molecules were used to reveal which ones are involved in the effects of PAR2-cAP and/or IFN-γ at MCP-1 secretion by

human neutrophils and monocytes. The inhibitors were used in the following concentrations: rottlerin [inhibits protein kinase Cδ (PKCδ)] 5 μm; LY294002 [inhibits phosphoinositide 3 (PI3) kinase] 50 μm; SB203580 (inhibits p38 kinase) 1 μm; and JAK inhibitor I pyridone 6 (pan-JAK inhibitor) 500 nm. All inhibitors were dissolved in DMSO, so the vehicle DMSO (1 : 1000) was used as an additional control. Human neutrophils and monocytes were pre-treated with the inhibitors for 30 min and then PAR2-cAP (1 × 10−4 m) alone or in combination with IFN-γ (100 ng/ml) was applied for 28 hr (the maximum effect of the stimuli at MCP-1 release was noticed at this time-point). After treatment, cell culture supernatants were collected and

used to measure MCP-1 concentration by human CCL2/MCP-1 (R&D Systems) ELISA kit. Results are expressed as mean ± SEM. At least three BI 6727 independent experiments were performed. Statistical evaluation was performed by paired Galactosylceramidase two-tailed Student’s t-tests. Significance was set at P < 0·05.

Neutrophils and macrophages from PAR2-deficient mice have been shown to display a significantly reduced phagocytic efficiency of Pseudomonas aeruginosa compared with cells from wild-type animals.24 However, the ability of PAR2 agonist to enhance the phagocytic activity of human neutrophils and monocytes and to affect IFN-γ-stimulated phagocytosis has yet to be evaluated. To investigate whether PAR2 agonist might potentially enhance the IFN-γ-induced phagocytosis we first carried out the phagocytosis assay with FITC-conjugated killed S. aureus. The treatment of human neutrophils with either PAR2-cAP (1 × 10−4 m) or IFN-γ (100 ng/ml) alone led to a similar enhancement of the mean fluorescence intensity (MFI) of human neutrophils (increased by around 40 ± 7% compared with untreated cells), indicating that the phagocytic activity of treated neutrophils increased (see supplementary material, Fig. S1). The combined action of PAR2-cAP and IFN-γ did not enhance the phagocytic activity of neutrophils above that triggered by either agonist acting alone (combined treatment increased phagocytic activity by around 51 ± 12% as compared with untreated cells) (Fig. S1).

Although the absence of other Ig isotypes was not in agreement with this hypothesis,

we aimed to formerly exclude the possibility by performing Western blot analysis using a polyclonal anti-μ Ab. Western blot analysis of different amounts of purified IgM showed that we could detect down to 7.8 ng/lane of μ-chains. WT sera diluted 1/100 gave a signal corresponding to 250 ng/lane (Fig. 2B, upper). Since 20 μL were loaded per lane, this corresponded to a detection limit of 390 ng/mL learn more and 12.5 μg/mL μ-chains for purified and 1/100 diluted serum, respectively. Analysis of sera from three homozygous IgM (Fig. 2B, middle) or two JH (Fig. 2B, lower) KO rats showed undetectable levels of IgM (<7.8 ng/lane) and thus below 12.5 μg/mL in serum. Sera from heterozygous IgM KO rats analyzed by Western blot showed normal

size and concentration of μ-chains (data not shown). These results indicated that both the IgM Cμ1 and the JH mutation resulted in a complete absence find more of the production of all Ig isotypes. The size of the spleens of IgM and JH KO rats was drastically reduced, whereas only some, but not all lymph nodes appeared to be slightly reduced. Thymus did not show obvious diminution (Fig. 3A). JH KO rats displayed an identical lymphoid organs macroscopic phenotype (data not shown). Immunohistology showed that spleens of IgM KO rats were completely devoid of CD45RA+ B (Fig. 3B) and IgM+ B cells (data not shown). As compared with WT animals, the TCRαβ+ T-cell zones of IgM KO rats were well defined but reduced in size and a matching reduction was also seen for CD4+ and CD8+ T cells (Fig. 3B). Lymph nodes also showed a complete absence of CD45RA+ B (Supporting Information Data 3) and of IgM+ B cells (data not shown) but normal areas of TCR+, CD4+ and CD8+ cells (Supporting Information Data 3). Thymus also showed the absence of small G protein-coupled receptor kinase clusters of CD45RA+ B cells and normal areas of TCR+, CD4+ and CD8+ cells (Supporting Information Data 3). JH KO rats showed identical lymphoid organ histology

(data not shown). These results indicate that B cells were virtually absent from secondary lymphoid organs in IgM and JH KO rats and as previously described for μMT KO and JH KO mice the number of T cells in spleen but not in lymph nodes or thymus was decreased 12, 14, 15. To better define the blockade in B-cell differentiation and to quantify the absolute numbers of different cell subsets, we evaluated the single-cell composition in the various lymphoid organs. Using CD45R (B220) and IgM as markers, several B-cell populations could be identified in the rat 16; pro–pre B (IgM− CD45Rlow), immature (IgMlow CD45Rlow), transitional (IgMhigh CD45Rlow), marginal zone (IgMhigh CD45R−) and mature (IgMlow and high CD45Rhigh). The analysis of IgD allowed a further subdivision of IgM+ B cells as IgDlow/− marginal zone and IgD+ follicular B cells and IgMlow IgD− as immature/transitional B cells 17.

In this model, the IL-12 family members had strikingly differential roles: while IL-23 was nonredundant for the development of colitis, only IL-12 perpetuated the Saracatinib cell line accompanying

systemic inflammatory response and wasting disease. The cell type responsible for the CD40-driven intestinal inflammation was not identified until recently, when Powrie and colleagues showed that a novel population of gut-resident Thy1+ Sca1+ RORγt+ innate lymphoid cells (ILCs) responds to IL-23 [98]. Mechanistically, IL-23R signaling activated expression of IFN-γ and IL-17 by ILCs, and neutralization of these cytokines strongly ameliorated the disease course [95]. Depletion of ILCs using an anti-Thy1 antibody almost abrogated colon inflammation, while the systemic wasting disease remained unaffected. When comparing the action of IL-23 on αβ T cells, γδ T cells, and ILCs, there seems to be a remarkable conservation in function, with all three cell types responding to IL-23 by production of proinflammatory cytokines such as IL-17, IL-22, and IFN-γ (Fig. 2). Thus, innate cells such as ILCs might be part of an early, immediate tissue inflammatory response, while T cells respond to IL-23 later in an antigen-dependent fashion. Of note, the (at least partially) IL-23-driven effector cytokines IL-17 and IFN-γ seem to play

completely divergent roles in different autoimmune settings: while neither of these cytokines are essential for disease Tanespimycin price progression in EAE [55, 56, 99], their neutralization in innate IBD strongly ameliorated the disease [98]. These differential results of cytokine depletion do not come as a surprise MycoClean Mycoplasma Removal Kit given the distinctive lymphocyte composition in the brain and the gut, but emphasize that the downstream effects of IL-23R engagement are highly dependent on the targeted cell population and the target organ. Very recently, it has been suggested that ILCs could also contribute to skin inflammation by IL-23-driven production of IL-22 [84]. However, whether IL-23-mediated activation

of ILCs is involved in additional immunopathologies remains to be determined and requires a more thorough understanding of the function of ILC populations during immune responses. When considering self-reactivity of the immune system and autoimmune destruction of healthy tissues, one must also consider the beneficial aspect of anti-tumor immunity [100]. T cells are known to play an important role in early-stage control of tumor growth, and some T-cell-derived cytokines such as IL-17 and IFN-γ are thought to have anti-tumor activity. For this reason, IL-23 has also been studied for its potential function during an anti-tumor response. Initial reports using IL-23-transfected tumor cell lines suggested an anti-tumorigenic function similar to that of IL-12 [101].

Thus, the vasculature in placental specimens must be perfused with X-ray opaque contrast agents (described in detail elsewhere [42, 37]) and imaged ex vivo to generate 3D data sets (Figure 2). Specimens with incomplete filling may be detected grossly during perfusion or upon visual examination of micro-CT images [37] and these can be excluded, which reduces the impact of this problem. The fetoplacental vasculature

is not innervated [34], so vascular tone is regulated selleck kinase inhibitor by local or circulating factors and these will be altered in ex vivo conditions. However, the inclusion of xylocaine in the perfusion medium [42, 37] appears to be largely successful in controlling ex vivo vasospasm such that umbilical artery diameters measured ex vivo using micro-CT are nearly identical to those measured in vivo using micro-ultrasound

[37]. Nevertheless, due to the requirement for vascular perfusion, artifacts due to incomplete filling or altered vascular tone cannot be ruled out. Branching patterns are varied and complex; even arterial trees that share identical genetics and the same intrauterine environment exhibit variation PARP inhibitor in arterial branching. Thus, quantitative geometric information is necessary to permit branching patterns of arterial trees to be statistically compared, and to predict the effect of different branching patterns on hemodynamics. Individual vessel segments, which are defined as the segment of vessel located between two branch points, are evaluated during automated image

segmentation analysis to determine their diameter, length, and position within the tree (Figure 3). There are more than 1000 vessel segments in late gestation in the fetoplacental arterial tree [36, 35]. One metric used to quantify the branching pattern is the length to diameter ratio, which describes how segment lengths change in relationship with vessel diameter throughout the tree. Another is the diameter scaling coefficient, which relates parent and daughter vessel diameters to show how quickly arterial diameter diminishes with successive branch generations. A metric that is particularly useful when evaluating developmental changes or differentiating vascular phenotypes is the number of vascular segments and their click here distribution as a function of vessel segment diameters (Figure 4C). The more specialized metric, vessel tortuosity, has proven useful for describing a vascular phenotype caused by environmental toxins [35]. As the arterial tree branches, and vessel diameters become smaller, one reaches a point where the vessel diameter is comparable to the image resolution and beyond which the image intensity of vessels drops rapidly. While high contrast objects that are smaller than the image resolution are in principle detectable, for typical scan protocols and contrast agents the smallest detected vessel will be comparable in size to the point-spread function, a measure of resolution, for the scanner.

The gene for TNF is polymorphic. Several TNF promoter SNPs have been reported to be associated with disease in humans. DNA sequence variations modifying transcriptional regulation of gene [154] play important role in many complex diseases. The first 200 bp of the

promoter are highly conserved across a range of species, with the murine, bovine and porcine promoters showing approximately 80% homology with the human promoter; while further upstream, there is far less conservation Fulvestrant mw between species. It has been reported that TNF rs1800630 polymorphism was associated with reduced level of serum TNF-α, because this polymorphism is strongly influence the binding of nuclear proteins [158]. In gene expression, the multiple TFs first assemble at the promoter site and the recruit RNA polymerase. These TFs bind to their cognate binding sites in the promoter region. The presence of polymorphism in regulatory region affects the interaction of TFs with transcription factor–binding site (TFBS), influencing

the expression of gene and thus susceptibility/resistance to disease. We have also predicted several SNPs in the promoter of TNF-alpha, computationally, which lies in TFBS of several TFs in upstream region of TNF-alpha (Table 4). Therefore, we hypothesized that predicted SNPs interfere with gene regulation FK506 in vivo and will increase the susceptibility to disease. Tumour necrosis factor promoter polymorphism and susceptibility to falciparum malarial infection and pulmonary tuberculosis have been carried out in Indian population. In malaria, TNF-α rs1799964 C and rs1800630 A-alleles as well as homozygotes for the TNF enhancer haplotype CACGG correlated with enhanced plasma TNF levels in both patients and controls. Significantly, higher TNF levels were observed in patients with severe malaria. In tuberculosis, no significant

differences of the allele frequencies between the patients with tuberculosis and controls have been reported but a significant difference in the serum TNF-α level in the patients and the controls has been found. Two TNF polymorphisms rs1800629 and rs361525 show association in most of the diseases (if Methamphetamine any association found). Probably, these polymorphisms affect the transcription of gene. Polymorphisms of TNF are likely to contribute to disease, the complex pattern of associations that has been revealed could also be attributable to LD with another susceptibility locus in the vicinity of the gene. By examining LD patterns, we determined that the effect of TNF is independent of the known HLA–A and HLA–DRB1 associations (Fig. 4). The chromosomal region surrounding TNF, however, is abundant in genes of immunologic relevance. To identify true susceptibility genes, the genetic variation of the region must be studied, and extended haplotypes must be constructed and analysed.

The phosphorylation of L-plastin relies on T-cell costimulation 8, 9, which Doxorubicin cell line means it is dependent on signals from the TCR/CD3 receptor complex as well as from signals that origin from accessory receptor. The inhibition of L-plastin phosphorylation by dexamethasone could be

reverted by the synthetic steroid mifepristone, which shows a glucocorticoid receptor dependency 36. Thus, effects of dexamethasone on L-plastin phosphorylation are most likely due to gene expression, suggesting an interference with the signaling pathway upstream of L-plastin phosphorylation. It is known that dexamethasone inhibits proximal signals induced by TCR triggering 37–40. In addition, dexamethasone could interfere with CD28-mediated signals. PI3K activity was shown to be involved in CD28-mediated costimulation 41–43 Veliparib supplier and its inhibition interferes with L-plastin phosphorylation in immune complex-stimulated

PMN 44. Dexamethasone inhibits PI3K in mast cells 45, which suggests PI3K and its inhibition might be involved in L-plastin phosphorylation upon T-cell costimulation. However, the relevance of dexamethasone for CD28-mediated PI3K activation in primary human T cells remains to be determined. One function of costimulation is the receptor movement to the immunological synapse 7, 12. Consequently, interference with L-plastin expression 5 or phosphorylation (this study) disturbed LFA-1 accumulation in the immune synapse. Interestingly, the effects on the accumulation of CD3 were much weaker and not significant in 5A-LPL-expressing T cells. It was therefore tempting to speculate that L-plastin phosphorylation Bacterial neuraminidase plays a role in peripheral SMAC, but not in central SMAC formation. The fact that 5E-LPL expression rescued only the LFA-1, but not the CD3 enrichment in dexamethasone-treated T cells strengthened that assumption. Interestingly, migration

of the TCR/CD3 complex toward the central SMAC depends on the actin cytoskeleton, as shown by the application of mycotoxins (e.g. cytochalasin D) 2. However, although 5A-LPL expression led to a lower F-actin content in stimulated T cells, the CD3 accumulation was not significantly disturbed. This might be due to the mode of inhibition of the actin cytoskeleton. Thus, in contrast to 5A-LPL expression, the application of mycotoxins to inhibit the actin cytoskeleton does not take into account the complex and spatio-temporal regulation of the actin cytoskeleton. In contrast to 5A-LPL expression, dexamethasone inhibits both the enrichment of the central SMAC-marker CD3 and the peripheral SMAC-marker LFA-1 in the immune synapse significantly. The difference between 5A-LPL expression and dexamethasone treatment on the CD3 enrichment in the immune synapse could be due to additional effects of dexamethasone on the actin cytoskeleton or signaling cascades.

Moreover, together with alterations in other markers of thymopoiesis which have been reported to occur predominantly in younger patients with MS, such SAHA HDAC research buy as reduced content of signal joint T-cell

receptor excision circles (sjTRECs) in peripheral T cells, decreased numbers of circulating RTEs defined by surface expression of CD31 and accelerated exit of CD4+ RTEs from the thymus as reflected by increased expression of CXCR4 in naïve and RTE CD4+ T-cell subsets, favor the hypothesis that premature thymic involution and immunosenescence play a role in disease pathogenesis 2–4, 6, 30. Autoimmunity associated with rheumatoid arthritis, systemic sclerosis (SS), and MS has been reported to concur with slow recovery of CD4+ T-cell counts after iatrogenic lymphopenia 31. Whereas a lacking IL-7 response accounts for this phenomenon in RA 31, it is this website thus far unexplained why T-cell immune reconstitution is delayed in patients with MS after therapeutic lymphocyte depletion with alemtuzumab (Campath-1H) 32, 33. The overall reduced IL-7Rα-expression on total Tconv and Tconv subsets in patients compared to healthy donors, as demonstrated in this study is well in line with the postulated failure in lymphocyte homeostasis. In lymphopenic patients

with MS this condition is likely to account for slower IL-7/IL-7R driven homeostatic lymphocyte proliferation and expansion. While the IL-7 response induced by lymphopenia following autologous stem cell transplantation 34 or alemtuzumab treatment 33 as Branched chain aminotransferase well as basal pretreatment serum IL-7 levels were reported to be unaltered in patients with MS and systemic sclerosis, we detected elevated plasma IL-7 concentrations in our cohort of patients with an established relapsing remitting type of disease. Since MS patients are not lymphopenic, we speculate that the production of IL-7 by non-hematopoietic stroma cells is upregulated as a consequence of the reduced

availability of IL-7Rα on patient-derived Tconv. In favor of this hypothesis, we found an inverse correlation between IL-7 levels and IL-7Rα-MFIs on total Tconv. Finally, we assessed the relative frequency of the rs6897932-SNP [T244I] located in exon 6 of the IL-7RA locus, which has been independently confirmed to be associated with MS 15–17 and also influences the risk of type 1 diabetes 18 and chronic inflammatory arthropathies 19. In agreement with the results reported in several large genetic association studies, the (C) allele encoding threonine instead of isoleucine at amino acid position 244 was enriched among patients and detectable in 74.7 versus 79.5% individuals in the groups of HC and patients respectively.

05) to adhere to human alveolar (A549) and human

bronchial (BBM) epithelial cells. The XDR variant of KZN invaded A549 cells more effectively than the other isolates. These results suggest that the successful spread of the Beijing and KZN strains might be related to their interaction with alveolar epithelium www.selleckchem.com/products/ensartinib-x-396.html (Ashiru et al., 2010). Examples of the locally predominant, but drug-susceptible clonal groups emerge, intriguingly, from the insular settings. In Japan, a large-scale study of the Beijing genotype revealed that the spread of its modern Beijing sublineage, which has a high transmissibility, is currently increasing, while the spread of an ancient Beijing sublineage has decreased significantly in younger generations (Iwamoto et al., 2009). In another study in Trinidad island in Caribbean, it was shown that a single major clone of an ‘evolutionary modern’ tubercle bacilli (SIT566) was responsible for more than INCB024360 nmr half of the TB cases, whereas it preferentially infected younger age groups. A comparison with genotyping data for six Caribbean countries showed that the overall lineage distribution in Trinidad was completely different from its neighbors, i.e., Trinidad was the only country harboring a unique sublineage of the LAM family, designated

LAM-10CAM (Millet et al., 2009). This sublineage is phylogeographically specific for Cameroon and neighboring countries in West Africa; it was shown to be significantly associated with clusters, suggesting its preponderant role PJ34 HCl in recent transmission in Cameroon (Niobe-Eyangoh et al., 2004) and Burkina Faso (Godreuil et al., 2007). Interestingly,

3/4 of the patients within this group in Trinidad were African descendants (Millet et al., 2009). As mentioned above for the case of Beijing and KZN families in South Africa, the locally predominant clones may be noncompetitively cocirculating in an area. In Tunisia, >60% of the TB cases were due to a single genotype in each prevalent family, although their clustering differed: more clustered ST50/Haarlem was more predominant in the northern Tunisia, while the more widespread ST42/LAM displayed weak clustering and a low transmission rate, suggesting its stable association with the Tunisian population (Namouchi et al., 2008). Regarding interpretation of the results in our study, it should be noted, however, that ST125 was not associated either with drug resistance (Valcheva et al., 2008a) or with a higher growth rate in mouse macrophage model (N. Markova et al., unpublished data). The ability to replicate rapidly within macrophages may be considered as a proxy for increased transmissibility (Nicol & Wilkinson, 2008). Therefore, the presence of ST125 in Bulgaria cannot be attributed to the increased resistance/virulence/transmissibility properties. Instead, the specificity of ST125 in Bulgaria probably reflects its historical presence in this region, leading to a bacterium–host coadaptation.

It induces the production of acute-phase proteins as well as infiltration of neutrophils. Because the expression of cytokines varies over time, one must always be aware of the timing when comparing studies. Chlamydiales infect epithelial cells as well as cells of the immune system. The combination of cytokines is distinct for each cell type, but different

concentrations and different cytokines are also observed for a single cell type depending on the experimental setup. The levels of cytokines expressed vary according to the species and/or serovars studied. A selection of cytokines and chemokines induced by chlamydial infections in different cell types is depicted in Table 1. For example, C. trachomatis infects the epithelial cells present in the reproductive tract of females. To NVP-BKM120 research buy study the cytokine expression elicited by these cells, mainly cancerous cell lines and primary cells were used. In cervical Dorsomorphin mouse HeLa cells (229), very different concentrations of IL-8, IL-1α and IL-6 were detected at the same infectivity ratio by Rasmussen et

al. (1997) compared with Dessus-Babus et al. (2000). In primary uterine cells, the basal expression of these cytokines was much closer to the uninfected nonpolarized cells than to the polarized cells (Fahey et al., 2005). This observation is counterintuitive because embedding in an extracellular matrix (ECM) gel should provide a more physiological setup shown by Dessus-Babus et al. (2000). This difference might be explained by the fact Vasopressin Receptor that the cancerous cell line used by Dessus-Babus et al. (2000), HeLa 229, is a subclone of HeLa (CCL2) used by Rasmussen et al. (1997). It is important to keep in mind that, depending on the tissue, not all detected cytokines are solely involved in innate immunity. Uterine epithelial cells continuously express cytokines, such as IL-6, IL-8 and TNF-α, to keep up an innate immune surveillance (Fahey et al., 2005). Furthermore,

some cytokines have been implicated to play a role in controlling the ovulatory cycle in coordination with leukocytes (García-Velasco & Arici, 1999). This is especially important when looking at data from in vivo studies. Chlamydia pneumoniae infects pneumocytes (murine) and induces the production of TNF-α and MIP-2 (Wissel et al., 2005). Interestingly, cell viability was not affected by cytokine secretion or by infection per se. Parachlamydia acanthamoebae also infects epithelial cells (pneumocytes) and no cytopathic effect could be observed either (Casson et al., 2006). One might assess whether the same cytokines are induced by C. pneumoniae and P. acanthamoebae to determine their possible role in protection against cytopathogenicity. Possible differences could be due to species or strain specificity, because cytokine profiles seem to be dependent not only on the cell type but also on the Chlamydia species and/or the serovar used for the experiment.

Some of the mechanisms by that endotoxin can mediate its effects include neutrophil and eosinophil recruitment as well as the activation of macrophages [3, 5, 6]. Chemically, endotoxins consist of lipopolysaccharides (LPS) that exert their effects via the CD14 receptor, a 53-kDa surface glycoprotein [7] expressed on monocytes, macrophages, granulocytes and B lymphocytes [5, 6]. The molecular

interactions underlying the binding of LPS have been extensively studied in recent years. Accordingly, LPS-binding protein (LBP) facilitates the binding of LPS in combination with CD14 to a receptor complex, which consists NVP-LDE225 chemical structure of Toll-like receptor-4 (TLR-4) and MD-2 [8–10]. The activation of the TLR induces an intracellular

signalling cascade, which results in the release of cytokines such as interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α [6, 11] which have also been shown in elevated concentrations in asthma [12–14]. In vitro, CD14 is constitutively released from mononuclear cell cultures as soluble CD14 (sCD14) [15, 16]. sCD14 can be found in two isoforms, a 49- and a 55-kDa protein. The 55-kDa isoform is produced by a shedding mechanism while the 49-kDa form is thought to derive from the interstitial space [16, 17]. The 49-kDa isoform is found in healthy subjects and is significantly elevated in patients with Selleck MLN0128 sepsis [18], polytrauma [19] and atopic dermatitis [20]. Shedding is increased by LPS and TNF-αin vitro [21] and also in vivo [22]. The click here function

of sCD14 has been associated with the activation of cells which do not possess membrane-bound CD14 [8]. Elevated levels of sCD14 have been found in bronchoalveolar lavage in several diseases such as tuberculosis, sarcoidosis, allergic alveolitis and idiopathic pulmonary fibrosis [6, 23–27]. sCD14 also seems to play a role in allergic asthma. Dubin et al. [28] showed an increase in sCD14 in bronchoalveolar lavage fluid (BALF) 24 h after allergen provocation which was confirmed by others [29]. Increased concentrations were also found in children with status asthmaticus [30]. In addition, CD14 expression has been correlated to the influx of neutrophils into the airways [22]. It has been suggested that this might be related to a remodelling processes in the airways as has been shown in an animal model with endotoxin-sensitive mice [31]. Moreover, distinct gene-polymorphisms of the C14 gene have been associated with an increased risk to develop an atopic phenotype [32]. It can therefore be hypothesized that an elevated expression of the LPS receptor might be involved in the activation of the inflammatory cascade in asthma which could lead to chronic inflammation, remodelling of the airways and subsequently an accelerated loss in FEV1.