Most of the piglets seroconverted to PCV2 between 28 and 35 days post vaccination and, although not all the animals had seroconverted by the time of challenge, they were all protected against subsequent PCV2a challenge, suggesting that strong

PCV2 antibody responses are not entirely necessary for protection (39). IM administration of a live PCV1-2 vaccine has also been demonstrated to be effective in conventional (41) and in SPF pigs (42). Similarly, combined IM and intranasal administration of live PCV2 vaccine reduced PCV2 viremia and associated lesions after challenge in SPF pigs (40). In our study, the majority of IM vaccinated pigs (21/28) had seroconverted four weeks after vaccination, which is in agreement with previous studies (39, 40, 42). In contrast, among all the PO vaccinated pigs, only 1/28 pigs had seroconverted by four weeks post vaccination. The limited ability of the experimental live-attenuated PCV1-2 vaccine to induce a measurable systemic antibody Ku 0059436 response may be due to limited absorption and replication. Nevertheless, as evident from the PO-non-challenged

group, PCV2 antibodies continued to increase beyond 4 weeks, indicating a delayed antibody response with the PO route of vaccination. Development of mucosal immunity by assessing presence of locally secreted PCV2 specific antibodies (for example in fecal supernatants) was not investigated, but may have given further insights into the effectiveness of this route. In this study, PCV2 DNA in sera was detectable in all treatment groups challenged with PCV2b. This is in contrast Torin 1 to previous studies where

PCV2 DNA was not detectable in vaccinated animals after challenge (39, 42). These conflicting results may 6-phosphogluconolactonase be due to differences between studies in the detection methods for PCV2 DNA. For instance, the real-time PCR assay used in the current study is more sensitive than the gel-based PCR assay used previously (39). Other differences between studies include the utilization of a heterologous PCV2b challenge strain in the current study in contrast to a homologous PCV2a challenge strain used in a previous study (39). Significant differences in prevalence and amount of PCV2 DNA, with a reduction of the amount of PCV2 DNA in sera ranging from 79.2% to 84.6%, were found in pigs vaccinated IM compared to non-vaccinated pigs. Moreover, only 21.4% of pigs vaccinated by the IM route were PCV2 viremic after PCV2 challenge. Among the IM vaccinated pigs that had no detectable seroconversion prior to challenge, subsequent PCV2 viremia was not observed in 1/3 IM-PCV2-I pigs and in 3/3 IM-PCV2-PRRSV-CoI pigs, indicating evidence of protection and strengthening the importance of cellular immune response. The amount of PCV2 DNA in sera was also reduced in pigs vaccinated PO; however vaccine efficacy in the PO vaccinated groups as measured by decreased incidence and degree of viremia was not as impressive as that of the IM vaccinated groups.

Therefore, we wondered whether TSLP expression

in human IECs was regulated in a similar fashion. Although we also observed that TSLP was regulated by NF-κB in Caco-2 and HT-29 cell lines in response to IL-1, we found contradictory results concerning the precise promoter site responsible for the NF-κB-dependent regulation of TSLP. The in silico analysis of a 4 kb-long region of human TSLP promoter allowed us to identify four potential NF-κB sites. Although human and murine TSLP promoters do not share significant Venetoclax sequence homology, one of these putative sites is conserved in mice TSLP promoter as well as in other mammals. Moreover, in mice a site corresponding to NF2 exerts the same biological function as that observed Cytoskeletal Signaling inhibitor in human

TSLP regulation and expression (P. Chambon, unpublished data and [36]). In our study, we used different strategies to demonstrate that NF2, a newly identified NF-κB responsive element located in the proximal region of TSLP promoter, is functionally important for the NF-κB-dependent regulation of human TSLP in IECs. We also demonstrated the functional importance of NF2 in regulating TSLP expression in other epithelial cells, including lung, cervical and kidney epithelial cells. Despite the fact that both NF1 and NF2 sites showed similar binding capacities for p65 and p50 subunits of NF-κB, as revealed by EMSA experiments using nuclear extracts from IL-1-, TNF- or PMA- stimulated Caco-2 and HT-29 cells, they produced a different impact on TSLP modulation. First, we assumed that both NF1 and NF2 sites were necessary to support the full transcriptional activity

of NF-κB complexes in response to the different ligands. However, TSLP promoter lacking a functional NF1 site was still able to respond to IL-1 in IECs as well as in other epithelial cells, including the lung cell line, A549, which has Sucrase been used in the previously published paper [16]. By contrast, all the IL-1-induced activity was lost following NF2 site mutation, demonstrating the absolute requirement of NF2 for the NF-κB-dependent regulation of TSLP driven by IL-1. We speculate that the presence of two NF-κB sites, one of which fails to respond to inflammatory agonist IL-1, could be necessary for constitutive expression of TSLP, while the other responses to upregulate TSLP expression under specific conditions. Overall, our data did not reveal other regulatory elements, other than NF2, that are absolutely essential for the IL-1-induced expression of TSLP. In accordance with previous studies [16, 17], we showed that TSLP promoter contains several putative AP-1 binding sites. These sites either cooperate with NF-κB sites to mediate the effects of IL-1 via ERK pathway or are involved in PKC signaling via PMA.

130 Rizza et al.131 predicted that IFN-α itself, as well as IFN-α-conditioned DC, can represent valuable components in the coming years of new and clinically effective protocols of therapeutic vaccination in patients with cancer and some chronic infectious diseases, whose immune suppression status can be restored by a selective use of these cytokines targeted to DCs and specific T-cell subsets under different experimental conditions. In chronic

HCV infection, virus-specific dysfunctional CD8 T cells often over-express various inhibitory receptors. Programmed cell death 1 (PD-1) was the first among these inhibitory receptors that were identified to be over-expressed in functionally impaired T cells. The roles of other inhibitory screening assay receptors such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) have also been demonstrated in T-cell dysfunctions that occur in patients Selleck Ulixertinib with chronic HCV infection. Blocking these inhibitory receptors in vitro restores the functions of HCV-specific CD8 T cells and allows enhanced proliferation, cytolytic activity and cytokine production. Therefore, the blockade of the inhibitory receptors is considered as a novel strategy for the treatment of chronic HCV infection.132 Recently, Zhang et al.133 demonstrated that up-regulation of PD-1 and suppressor

of cytokine signalling-1 (SOCS-1) correlates with IL-12 inhibition by HCV core protein and that blockade of PD-1 or SOCS-1 signalling may improve TLR-mediated signal transducer and activator of transcription 1 (STAT-1) activation and IL-12 production in monocytes/macrophages. Blocking PD-1 or silencing SOCS-1 gene expression also decreases Tim-3 expression and enhances IL-12 secretion and STAT-1 phosphorylation.134 These

findings suggest that Tim-3 plays a crucial role in negative regulation of innate immune responses, through cross-talk with PD-1 and SOCS-1 and limiting STAT-1 phosphorylation, and may be a novel target for immunotherapy to HCV infection. The high levels of IL-10 present in chronic HCV infection 2-hydroxyphytanoyl-CoA lyase have been suggested as responsible for the poor antiviral cellular immune responses found in these patients. To overcome the immunosuppressive effect of IL-10 on antigen-presenting cells such as DC, Diaz-Valdes et al.135 developed peptide inhibitors of IL-10 to restore DC functions and concomitantly induce efficient antiviral immune responses. The results suggest that IL-10-inhibiting peptides may have important applications to enhance anti-HCV immune responses by restoring the immunostimulatory capabilities of DC. Regulatory T cells (Treg cells) suppress autoreactive immune responses and limit the efficacy of vaccines, however, it remains a challenge to selectively eliminate or inhibit Treg cells.

This calls into question the applicability to the human situation of studies performed on the lower genital tract in animal models. In addition, the observed failure of HCl to substitute for lactic acid suggests the specificity of lactic acid, and not just an acidic pH, for IL-23 induction. Thus, experimental protocols as well as commercial products that attempt to acidify the vagina with acids other than lactic acid do not mimic the natural environment and may be less than ideal. The implication that lactic acid may specifically aid selleck inhibitor in immune defense

leads one to question currently held beliefs about vaginal health. Vaginal lactic acid production by both the underlying epithelium (Gross, 1961) and endogenous lactobacilli and other bacteria contribute

to the final lactic acid concentration. Individual differences in colonizing lactobacilli and other components of the vaginal flora, variations in the genetic background that influence glucose metabolism and unique ABC294640 concentration environmental and dietary exposures would all be expected to result in variations in lactic acid production. We postulate that the extent of lactic acid production, and not bacterial hydrogen peroxide production, is a key component of the innate immune defense mechanisms at this site. A recent investigation using gene amplification technology has revealed that the major Lactobacillus sp. in asymptomatic North American women is Lactobacillus inners, a bacterium that does not produce hydrogen peroxide (Ravel et al., 2010). Another study has demonstrated that both cervicovaginal fluid and semen block any hydrogen peroxide-induced microbicidal activity (O’Hanlon et al., 2010). Further study of larger numbers of women is clearly warranted to confirm our findings as well as to help unravel the misconceptions that now exist about vaginal bacterial flora and innate defense mechanisms

at this anatomical site. It would also be of interest to determine whether other organic acids that are structurally related to lactic acid, and that may be present in the vagina, have similar immunological Oxymatrine effects. In this regard, it has been demonstrated that lactate, but not butyrate, acetate, dichloroacetate, citrate or malate, augments lipopolysaccharide-induced IL-2 production by murine splenic T cells (Roth & Droge, 1991). In females before puberty and after menopause, vaginal lactic acid levels are much reduced and vaginal pH is elevated. Whether this contributes to a possible increased susceptibility to gram-negative bacterial infections under these conditions is not known and is worthy of investigation. In general, mucosal infection favors the induction of the Th17 subset while intravenous infection is characterized by the induction of Th1 cells (Pepper et al., 2010). This suggests that antimicrobial immunity at mucosal surfaces is preferentially geared towards IL-23 and IL-17 induction and away from the production of Th1 lymphocyte-generated IFN-γ.

Consequently, in an attempt to initiate

a self-healing response, we adoptively transferred CCR7+ (B6.WT) DCs into the site of infection of B6.CCR7−/− mice. Surprisingly, instead of healing the lesion, B6.CCR7−/− mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7−/− mice transferred with B6.CCR7−/− DCs or see more B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7−/− DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major. “
“Signal regulatory protein α (SIRPα/CD172a), expressed by myeloid cells including CD11b+ dendritic cells, interacts with ubiquitously expressed CD47 to mediate cell–cell signalling and therefore, may be pivotal in the development of tolerance or immunity. We show that in mice deficient in CD47 (CD47−/−) the cellularity in gut-associated lymphoid tissues is reduced by 50%. In addition, the frequency of CD11b+ CD172a+ dendritic cells is significantly reduced in the gut and mesenteric this website lymph nodes, but not in Peyer’s patches. Activation of ovalbumin (OVA)-specific CD4+ T cells in the mesenteric lymph nodes after feeding OVA is reduced in CD47−/− mice compared with wild-type however, induction of oral tolerance is maintained. The

addition of cholera toxin generated normal serum anti-OVA IgG and IgA titres but resulted in reduced intestinal anti-OVA IgA in CD47−/− mice. Replacing the haematopoietic compartment in CD47−/− mice with wild-type cells restored neither the cellularity in gut-associated lymphoid tissues nor the capacity to produce intestinal anti-OVA IgA

following immunization. This study demonstrates that CD47 signalling is dispensable for oral tolerance induction, whereas the expression of CD47 by non-haematopoietic cells is required for intestinal IgA B-cell 5-FU manufacturer responses. This suggests that differential CD4 T cell functions control tolerance and enterotoxin-induced IgA immunity in the gut. The intestinal immune system has dual and opposing roles as it must discriminate between harmful substances, to generate an effector response, and benign food antigens, to maintain tolerance. A prominent feature of the intestinal immune system is the generation of IgA-producing plasma cells. Oral immunization with the powerful adjuvant cholera toxin (CT) is dependent on CD4+ T cells to generate antigen-specific IgA.1,2 Dendritic cells (DC) strategically placed beneath intestinal epithelial cells have been shown to be important for the induction of oral tolerance.3 They are essential for immunogenic functions including CD4+ T-cell activation and subsequent generation of antigen-specific antibodies following oral immunization with adjuvants.

Inflammation of the asthmatic airway is usually accompanied this website by increased vascular permeability and plasma exudation 1. Although other inflammatory mediators, including platelet-activating factor, can promote microvascular leakage 32, VEGF appears to be the critical mediator of vascular permeability in asthma 3, 16, 33, 34. The mechanism of VEGF-mediated induction of the vascular permeability seems to be the enhanced functional activity of vesiculo-vacuolar organelles 17, 33. VEGF can be produced by a wide variety of cells such as macrophages, neutrophils, eosinophils, and lymphocytes 3, 17, 33–35. Several studies

have shown that overproduction of VEGF causes an increase in vascular permeability, which results in leakage of plasma proteins, inflammatory mediators, and inflammatory

cells into the extravascular space thereby allowing migration of inflammatory cells into the airway 3, 33, 36. In addition, VEGF also plays a crucial role in adaptive Th2-mediated inflammation 17. Consistent with these observations, we have found that allergic airway disease of mice induced by OVA inhalation resulted in up-regulation of VEGF expression, increases in IL-4, IL-5, and IL-13 levels, and enhancement of vascular permeability. The increased VEGF, IL-4, IL-5, and IL-13 levels, vascular permeability, bronchial inflammation, and airway hyperresponsiveness were significantly reduced after administration of a VEGF receptor Isotretinoin inhibitor, CBO-P11. This inhibitor is a cyclic peptide of Selleck Autophagy inhibitor 17 amino acids derived from VEGF residue 79–93 and thus blocks binding of VEGF to its receptor, thereby VEGF signaling is obstructed 37. In addition, our previous studies with a murine model of asthma have revealed that the VEGF receptor tyrosine kinase inhibitors SU5614 and SU1498 reduce asthmatic features such as the increase in Th2 cytokines, VEGF,

vascular permeability, inflammatory cells in airways, and airway hyperresponsiveness 3, 38, 39. Together, these findings suggest that VEGF is a key player in inducing and maintaining allergic airway disease. HIF-1α regulates VEGF expression, and activation of HIF-1α is controlled by a variety of inflammatory cytokines and growth factors as well as by cellular oxygen concentrations 7. Very recently, we have shown that increased expression of VEGF after OVA inhalation is decreased by administration of an HIF-1α inhibitor 9. In keeping with these observations, determination of HIF-1α protein levels in nuclear extracts in this study revealed that this protein is substantially increased in our current mouse model of OVA-induced allergic airway disease and tracheal epithelial cells isolated from OVA-treated mice, suggesting that HIF-1α is activated. The increased levels of HIF-1α were significantly reduced after administration of 2ME2 or transfection of siRNA targeting HIF-1α.

Whether type I IFNs also regulate

IL-10 through the FcγR pathway is not yet known and should be investigated, as depletion of CD25+ T cells did not change any of the important immunological parameters, parasite burdens, or lesion progression in our previous studies of L. mexicana infection in B6 mice (22). IgG plays an important role in chronic disease in L. mexicana infection. IgG1, which AZD6244 nmr appears earlier than IgG2a/c, has a high affinity for FcγRIII, and immune complexes of L. mexicana amastigotes can induce IL-10 through this receptor (22). Mice lacking either IL-10 or FcγRIII heal their lesions and have many orders of magnitude fewer parasites with an associated enhanced

IFN-γ response (4,22). In the current studies, we found that IFN-α/βR KO mice had stronger Leishmania-specific IgG1 and IgG2a/c responses at 12 weeks of infection than WT mice, indicating that IFN-α/β directly or indirectly partially suppresses the IgG response, possibly by decreasing or slowing B cell proliferation or IgG secretion. The stronger effect is on IgG1, which is Forskolin nmr increased by >10-fold, with a 7-fold increase in IgG2a/c. Later, in infection, the increased IgG1 response could dampen the IFN-γ response by induction of IL-10 through FcγRIII, with suppression of Th1 development. In fact, we do see that the decrease in IFN-γ in IFN-α/βR KO mice resolves by 17 weeks of infection. Although IFN-γ is known to drive IgG2a/c and IL-4 to drive IgG1 class switching, the KO mice had no measurable change in IL-4 levels (which are very low) and actually had diminished IFN-γ production. Thus, IFN-α/β must be acting on IgG isotype selection through other undescribed pathways. Later, in infection, this enhancement of IgG in the KO mice was no longer evident, similar to the effects on IFN-γ.

At 4 weeks of infection, there is a weaker IFN-γ response in IFN-α/βR KO mice, and yet parasite loads are not different. This is consistent with several other studies in which early parasite loads (4–8 weeks) did not correlate with defects in various immunological factors such as IL-10 and FcγRIII despite early increases on IFN-γ (4,22), Ergoloid but parasite loads then dropped by 12 weeks of infection. This may be because of delays in T cell development and migration to the lesion. Later in infection, the T cell IFN-γ levels and IgG levels are comparable in IFN-α/βR KO and WT mice, consistent with the similar lesion sizes and parasite loads. As mentioned above, the IL-10 in lesions from IgG-FcγR pathways correlates better with parasite loads and lesion size than does LN T cell IL-10, and the lower IL-10 seen in IFN-α/βR KO at 17 weeks agrees with this assessment.

In parallel,

even when increased level of insulin in the umbilical cord blood is found in GMD [71], confirming earlier observations [22, 51, 99], there is not information regarding the potential mechanism(s) associated with this specific response to insulin by the fetoplacental unit in GDM [5, 81, 83, 101]. Abnormal regulation of the insulin receptor splicing in key tissues responsive to insulin may occur in patients with insulin resistance, but its role is unclear in GDM [50, 81]. A recent study shows that IR-A activation by insulin activates a predominant mitogenic instead of a metabolic signaling BGB324 pathway in HUVEC [98] (F Westermeier and L Sobrevia, unpublished observations), as described in response to IR-B activation in the R-cell line of mouse embryonic fibroblasts LY294002 [75]. These findings suggest differential cell signaling pathways activated by these insulin receptor subtypes in the human fetoplacental macrocirculation [35, 75]. Thus, modulation of the expression level of these isoforms will have a consequence in the metabolism of the endothelial cells of the fetoplacental unit in GDM. Other evidence suggests that decreased insulin response could result from increased IR-A over IR-B expression as reported in skeletal muscle of patients with type 2 diabetes

mellitus [63] and patients with myotonic dystrophy type 1 [73] or 2 [7, 73]. A potential insulin resistance in parallel with reduced insulin sensitivity and β-cell function in the human fetus from GDM pregnancies is reported [71]. Thus, differential expression of insulin receptor isoforms in fetoplacental tissues could be playing a

role in this DNA ligase phenomenon. There is not available information regarding functionality of the l-arginine/NO pathway or the expression of hCATs and eNOS in placental microvascular endothelium from GDM pregnancies [39, 81]. However, in hPMEC from normal pregnancies l-arginine uptake has been reported as mediated by system y+/CATs with apparent Km ~ 90 μM and system y+L with apparent Km ~ 2 μM [26]. Based on the apparent Km values detected in these assays, it was suggested that hCAT-1 isoform instead of hCAT-2A or hCAT-2B isoforms were responsible of l-arginine transport in this cell type. Interestingly, since hCAT-2B transport activity occurs with an apparent Km in a similar range of that for hCAT-1 activity in hPMEC (E Guzmán-Gutiérrez and L Sobrevia, unpublished observations) and most mammalian cells [24, 53, 81], complementary assays such as trans-stimulation of transport, or the use of tools leading to knockdown or overexpression of these membrane transporters, are required for a better discrimination between these two potential transport mechanisms. We have found that l-arginine transport is mediated by hCAT-1 and hCAT-2B in hPMEC from normal pregnancies, a phenomenon most likely under modulation by insulin (E Guzmán-Gutiérrez and L Sobrevia, unpublished observations).

Thirty years ago, Eμ was the first transcriptional enhancer discovered upstream of the μ gene (Fig. 1A) 1–3. Eμ deletion in mice confirmed its role in controlling access to the locus prior to D-J recombination, but, moreover, showed its dispensability for CSR and SHM 4. Eventually, several more transcriptional

enhancers were identified at the 3′ end of the locus. hs1,2 was identified 12.5-kb downstream of the mouse Cα (Fig. 1A) 5. It is as active as Eμ, and furthermore, is at the center of a more than 25-kb palindrome 6 bounded by two inverted copies of a weak enhancer: hs3a (2-kb downstream of Cα) PCI-32765 molecular weight and hs3b (29-kb downstream of Cα). A final enhancer, hs4, lies 4-kb downstream of hs3b 7. hs1,2, hs3a and hs3b are all active at late B-cell differentiation stages, while hs4 is active during the pre-B-cell stage and throughout B-cell development

(Fig. 1A) 8, 9. The modest activity of each of the 3′RR elements, however, contributes to a synergic and potent global effect of the 3′RR, especially when its “palindromic” architecture is maintained. In addition, the 3′RR elements also synergize with Eμ at the mature B-cell stage, whereas in pre-B cells, hs4 and Eμ do not. Transgenic models have clarified the onset of 3′RR activity (schematized in Fig. 1B). Its specific activity in B-cell lineages, initiated in pre-B cells, culminates at mature stages 10, 11. Knock-out animal models have helped elucidate the main 3′RR functions (Fig. 1C). For example, replacement of hs1,2 or hs3a with a neomycin-resistant gene broadly affected CSR 12, 13. However, subsequent deletion of this neo Selleck CHIR 99021 cassette restored a normal phenotype 13. Furthermore, knock-out of individual 3′ elements demonstrated that all of them are dispensable for CSR 13–15, most likely due to functional redundancies. Only hs4 deletion revealed a specific role for this

element IMP dehydrogenase in IgH expression in resting B cells 15. Indeed, combined deletion of both hs3b and hs4 affected CSR as a consequence of impairment of the Ig constant gene germline transcription to most isotypes (except γ1) 16. Recently the complete deletion of the 3′RR in large transgenes 17 or in the endogenous locus 18 showed that it is a master control element of CSR in all isotypes. Endogenous 3′RR-deficient mice clarified that 3′IgH enhancers play their most crucial role at the late stages of B-cell development. Thus, these mice harbored abundant B-lineage cells in all compartments. While plasma cells differentiated normally in 3′RR-deficient animals, antibody secretion was depressed for all Ig (including IgM), due to both the CSR failure and a global IgH transcription defect in plasma cells 18. In contrast to CSR, SHM and V(D)J recombination were grossly normal in 3′RR-deficient mice (Vincent-Fabert et al., manuscript in preparation).

Cleavage of fB by fD results in formation of the initial AP C3 convertase C3(H2O)Bb, which, like the classical C3 convertase C4bC2a, can cleave C3 into C3b and C3a. The generation of C3b allows the AP to be fully activated via formation of the bona fide AP C3

convertase Maraviroc solubility dmso C3bBb (Fig. 1). Newly formed C3bBb is stabilized by the plasma protein properdin that binds to the complex and slows its deactivation.4 In fact, it should be noted that while the spontaneously generated C3(H2O)Bb is unique to AP, the C3b fragment generated from any of the pathways can bind to fB and, with the participation of fD, can form the AP C3 convertase C3bBb, which serves as an amplification loop for the entire complement system by rapidly augmenting the conversion of C3 to C3b necessary for full activation of the system and its downstream effects (Fig. 1).4 The cleavage of C3 to C3b is therefore the key step of convergence in the activation of the complement cascade.3

Apart from initiating the AP complement, C3b attaches to cells or immune complexes through covalent bonding; the opsonization of these targets by C3b or its further cleavage fragments facilitates their transportation and disposal through the endoreticular system. Additionally, C3b can associate with either of the C3 convertases to form the C5 convertase that cleaves C5 into C5a and C5b and initiates the terminal complement cascade, ultimately resulting in the formation of the multimeric membrane attack complex (MAC) (Fig. 1). In contrast to the early steps of complement activation,

assembly of the cytolytic MAC on the cell surface CHIR-99021 chemical structure is a Forskolin nonenzymatic process, initiated by association of C6 and C7 to C5b and subsequent insertion of the C5b-7 complex into the cell membrane through a hydrophobic domain in C7.5 Further attachment of C8 and multiple copies of C9 to the membrane-residing C5b-7 leads to assembly of the MAC, which creates physical pores in the cell membrane and causes lysis.3,5 Although the above scheme of complement activation is well established, two recent findings have provided novel insight into the activation mechanism of the AP. Biochemical and gene-targeting studies have revealed a critical role of properdin in initiating AP complement activation on some, although apparently not all, susceptible surfaces.6–10 Accumulating evidence supports the conclusion that, in addition to serving as a stabilizer of C3bBb, properdin can function as a pattern recognition molecule to trigger AP complement activation and in some instances such an activity of properdin is indispensible for the AP.6,7 The second notable finding of recent studies is the requirement of MASP1/3 for normal AP complement activity.11 It has been shown that MASP-1/3 cleaves inactive fD zymogen into the active form of fD that is normally present in plasma.