16 research outputs found
Abnormal directed migration of blood polymorphonuclear leukocytes in rheumatoid arthritis. Potential role in increased susceptibility to bacterial infections.
Rheumatoid arthritis (RA) patients are at higher risks of bacterial infection than healthy subjects. Polymorphonuclear leukocytes (PMN) are the first line of nonspecific cellular defence against these infections. We tested the hypothesis that abnormal directed migration of PMN may be one reason for the increased infection rate of RA patients. PMN migration was investigated in 68 peripheral blood samples of 15 RA patients compared with 64 samples of healthy controls in a novel whole blood in vitro membrane filter assay. The migration of PMNs from RA patients and controls was stimulated using the bacterial chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Unstimulated PMN migration of RA patients was increased compared with healthy controls as measured by the following parameters: (a) absolute number of migrant PMNs (1954+/-87 vs. 1238 +/-58 PMN/mm2), (b) percentage of PMNs migrated into the filter (total migration index, TMI) (28.6+/-0.9 vs. 24.0+/-0.8%), (c) the distance half the migrating PMNs had covered (distribution characteristic, DC) (22.6+/-1.1 vs. 16.1+/-0.6 mm) and (d) the product of TMI and DC (neutrophil migratory activity, NMA) (669.0+/-45.0 vs. 389.0+/-18.9). fMLP stimulated PMNs of RA patients showed defective migration compared to unstimulated samples as shown by (a) a reduced number of migrant PMNs (1799+/-93 PMN/mm2), (b) lower TMI (26.1+/-0.9%), (c) unremarkable altered distribution characteristic (22.9+/-0.8 mm) and (d) significant reduced migratory activity (600.0+/-30.0). Our data suggest that the high incidence of infections in RA patients may partly be caused by defective migratory activity of PMNs to bacterial chemoattractants as demonstrated by fMLP
Neutrophils: the forgotten cell in JIA disease pathogenesis
Juvenile idiopathic arthritis (JIA) has long been assumed to be an autoimmune disease, triggered by aberrant recognition of "self" antigens by T-cells. However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA. In particular, new data suggest an important role for neutrophils in JIA pathogenesis. In this short review, we will discuss the new data that support a role for neutrophils in JIA, discuss regulatory functions that link neutrophils to adaptive immune responses, and discuss future areas of investigation. Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA
Nasal biomarkerâprofiles to distinguish between highâ and lowâsymptomatic, nonâallergic and allergic subjects in a natural pollen exposure study [Abstract]
Influence of elevated ambient CO2 on the sensitizing potential of ragweed (Ambrosia artemisiifolia) pollen.
Birch pollen induces toll-Like receptor 4-dependent dendritic cell activation favoring T cell responses.
Seasonal exposure to birch pollen (BP) is a major cause of pollinosis.
The specific role of Toll-like receptor 4 (TLR4) in BP-induced allergic
inflammation and the identification of key factors in birch pollen
extracts (BPE) initiating this process remain to be explored. This study
aimed to examine (i) the importance of TLR4 for dendritic cell (DC)
activation by BPE, (ii) the extent of the contribution of BPE-derived
lipopolysaccharide (LPS) and other potential TLR4 adjuvant(s) in BPE,
and (iii) the relevance of the TLR4-dependent activation of
BPE-stimulated DCs in the initiation of an adaptive immune response. In vitro,
activation of murine bone marrow-derived DCs (BMDCs) and human
monocyte-derived DCs by BPE or the equivalent LPS (nLPS) was analyzed by
flow cytometry. Polymyxin B (PMB), a TLR4 antagonist and TLR4-deficient
BMDCs were used to investigate the TLR4 signaling in DC activation. The
immunostimulatory activity of BPE was compared to
protein-/lipid-depleted BPE-fractions. In co-cultures of BPE-pulsed
BMDCs and Bet v 1-specific hybridoma T cells, the influence of the
TLR4-dependent DC activation on T cell activation was analyzed. In vivo
immunization of IL-4 reporter mice was conducted to study BPE-induced
Th2 polarization upon PMB pre-treatment. Murine and human DC activation
induced by either BPE or nLPS was inhibited by the TLR4 antagonist or by
PMB, and abrogated in TLR4-deficient BMDCs compared to wild-type BMDCs.
The lipid-free but not the protein-free fraction showed a reduced
capacity to activate the TLR4 signaling and murine DCs. In human DCs,
nLPS only partially reproduced the BPE-induced activation intensity.
BPE-primed BMDCs efficiently stimulated T cell activation, which was
repressed by the TLR4 antagonist or PMB, and the addition of nLPS to Bet
v 1 did not reproduce the effect of BPE. In vivo, immunization
with BPE induced a significant Th2 polarization, whereas administration
of BPE pre-incubated with PMB showed a decreased tendency. These
findings suggest that TLR4 is a major pathway by which BPE triggers DC
activation that is involved in the initiation of adaptive immune
responses. Further characterization of these BP-derived TLR4 adjuvants
could provide new candidates for therapeutic strategies targeting
specific mechanisms in BP-induced allergic inflammation
Changes in immunoglobulin levels under real-life pollen exposure: Role of nasal IgA and IgG antibodies.
Ragweed plants grown under elevated CO<sub>2</sub> levels produce pollen which elicit stronger allergic lung inflammation.
Background Common ragweed has been spreading as a neophyte in Europe. Elevated CO2 levels, a hallmark of global climate change, have been shown to increase ragweed pollen production, but their effects on pollen allergenicity remain to be elucidated.Methods Ragweed was grown in climate-controlled chambers under normal (380 ppm, control) or elevated (700 ppm, based on RCP4.5 scenario) CO2 levels. Aqueous pollen extracts (RWE) from control- or CO2-pollen were administered in vivo in a mouse model for allergic disease (daily for 3-11 days, n = 5) and employed in human in vitro systems of nasal epithelial cells (HNECs), monocyte-derived dendritic cells (DCs), and HNEC-DC co-cultures. Additionally, adjuvant factors and metabolites in control- and CO2-RWE were investigated using ELISA and untargeted metabolomics.Results In vivo, CO2-RWE induced stronger allergic lung inflammation compared to control-RWE, as indicated by lung inflammatory cell infiltrate and mediators, mucus hypersecretion, and serum total IgE. In vitro, HNECs stimulated with RWE increased indistinctively the production of pro-inflammatory cytokines (IL-8, IL-1 beta, and IL-6). In contrast, supernatants from CO2-RWE-stimulated HNECs, compared to control-RWE-stimulated HNECS, significantly increased TNF and decreased IL-10 production in DCs. Comparable results were obtained by stimulating DCs directly with RWEs. The metabolome analysis revealed differential expression of secondary plant metabolites in control- vs CO2-RWE. Mixes of these metabolites elicited similar responses in DCs as compared to respective RWEs.Conclusion Our results indicate that elevated ambient CO2 levels elicit a stronger RWE-induced allergic response in vivo and in vitro and that RWE increased allergenicity depends on the interplay of multiple metabolites