Biomedical subjects

Magnus Korsgren

Publications and source records attributed to Magnus Korsgren.

7 recordsLinked to original sources

PubMed2006

The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution.

Upon encounter with antigen, the B lymphocyte population responds by producing a diverse set of antigen-specific antibodies of various isotypes. The vast size of the responding populations makes it very difficult to study clonal evolution and repertoire composition occurring during these processes in humans. Here, we have explored an approach utilizing the H-EPSILON-encoding transcriptome to investigate aspects of repertoire diversity during the season of antigen exposure. We show through sequencing of randomly picked transcripts that the sizes of patients' repertoires are relatively small. This specific aspect of the transcriptome allows us to construct evolutionary trees pinpointing features of somatic hypermutation as it occurs in humans. Despite the small size of the repertoires, they are highly diverse with respect to VDJ gene usage, suggesting that the H-EPSILON-encoding transcriptome is a faithful mimic of other class-switched isotypes. Importantly, it is possible to use antibody library and selection technologies to define the specificity of clonotypes identified by random sequencing. The small size of the H-EPSILON-encoding transcriptome of peripheral blood B cells, the simple identification of clonally related sets of genes in this population, and the power of library and selection technologies ensure that this approach will allow us to investigate antibody evolution in human B lymphocytes of known specificity. As H-EPSILON repertoires show many of the hallmarks of repertoires encoding other isotypes, we suggest that studies of this type will have an impact on our understanding of human antibody evolution even beyond that occurring in the IgE-producing B cell population.

Amino Acid Sequence↗

PubMed2006

Onset of action of a topical antihistamine as assessed by histamine challenge-induced plasma exudation responses.

BACKGROUND: Although usually administered orally, antihistamines are available also for topical use in allergic rhinitis. Information on onset of action of these drugs is incomplete. OBJECTIVE: To examine onset of action of topical cetirizine-dinitrate on plasma exudation evoked by repeated nasal histamine challenges. METHODS: A liposome formulation of cetirizine-dinitrate (2.44 mg per nasal cavity) was delivered via a nasal spray device as 2 consecutive actuations per nasal cavity in a placebo-controlled design. The nasal mucosal surface was challenged and lavaged with a histamine solution (100 microg/mL) 5, 15, 25, and 55 minutes after each treatment. In addition, the mucosa was lavaged with saline before each treatment. The lavage fluid levels of alpha2-macroglobulin were measured as an index of mucosal exudation (luminal entry) of plasma. RESULTS: Histamine produced significant increases in nasal lavage fluid levels of alpha2-macroglobulin at all observation points (5 through 55 minutes after treatment). Nasal cetirizine-dinitrate significantly inhibited this response at 5 and 15 minutes after treatment. CONCLUSIONS: The effect of topical cetirizine-dinitrate, as established by histamine challenge-induced mucosal exudation of plasma, has an early onset (ie, within 5 to 10 minutes).

Administration, Intranasal↗

PubMed2005

Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals.

Dendritic cells (DCIs) possess a potent ability to modulate and activate specific T-cell responses to allergens, which play a pivotal role in allergic inflammation by secreting cytokines and other mediators. However, the molecular mechanisms by which allergen-challenged DCs regulate specific T-cell responses are still not well characterized. This study aims at elucidating the molecular mechanisms underlying the DC-T-cell interaction during an allergic immune response to grass pollen, using a genomic and functional approach. Transcriptional analysis was performed on grass allergen Phleum pratense-stimulated DCs and on autologous memory CD4(+) T cells co-cultured with allergen-challenged DCs from healthy and allergic donors. DCs from the allergic donors were potent inducers of T-cell proliferation and T(h)2 polarization, as demonstrated by high IL-4, IL-5 and IL-13, and low IFN-gamma production. A gradual up-regulation of activation markers on both DCs and T cells was evident during the co-culture period, demonstrating an educational element of the DC-T-cell interaction. The global transcriptional analysis revealed a differential gene regulation in DCs and T cells derived from allergic donors after stimulation with allergen, as compared with the healthy donors. Peripheral memory CD4(+) T cells from healthy and allergic donors also responded differently after stimulation with allergen-loaded DCs with respect to cytokine production, proliferation, surface marker expression and gene transcription. We found up-regulated genes involved in T(h)2 cell biology, such as genes important for homing, adhesion, signaling and transcription, in addition to genes previously not described in the context of allergy. The panel of differentially expressed genes in the allergic group will form the basis for an increased understanding of the molecular mechanisms in allergy.

Biomarkers↗

PubMed2003

Acute allergic responses induce a prompt luminal entry of airway tissue eosinophils.

Traditionally, traffic and activation of eosinophils in asthmatic airways are thought to take place during the late-phase allergic reaction. The present study tests the hypothesis that when eosinophils are present in the tissue before allergen exposure, as in chronically inflamed asthmatic airways, acute anaphylactic reactions initiate an eosinophil response. Using a guinea-pig allergic model, where eosinophilia is present at baseline conditions, the traffic of resident eosinophils was examined in vivo immediately after allergen challenge. By 2 min after challenge, eosinophils had moved up to apical epithelial positions. Within 10 min, a marked migration of eosinophils into the airway lumen was demonstrated. Along with the allergen-induced egression of eosinophils, acute luminal entry of plasma proteins and eotaxin occurred. Eosinophil egression was effectively inhibited by the antiexudative drug formoterol, whereas the proexudative drug bradykinin could in naive animals evoke a prompt luminal entry of eosinophils. In conclusion, the present study demonstrates that acute allergic reactions initiate a prompt transepithelial migration of resident eosinophils. Our data further suggest that this response in part is initiated by the plasma exudation response, which may alter the transepithelial gradient of eosinophil chemoattractants including eotaxin. We propose that prompt eosinophil response is a significant component of the acute phase of allergic reactions when occurring in airways where these cells are already present in the mucosa.

Acute Disease↗

PubMed2003

Neural expression and increased lavage fluid levels of secretoneurin in seasonal allergic rhinitis.

Secretoneurin is a neuropeptide potentially involved in migration of eosinophils, monocytes, and dendritic cells. Whether secretoneurin is present in the human airway mucosa and whether it is released at ongoing allergic airway inflammation is currently unknown. In patients with allergic rhinitis, we have explored the occurrence of secretoneurin in nasal mucosal biopsies and lavage fluids before and during natural allergen exposure. Immunohistochemical analysis revealed an abundance of nerves displaying secretoneurin immunoreactivity, which were distributed predominantly around blood vessels and submucosal glands. A majority of nerve fibers containing vesicular acetylcholine transporter, tyrosine hydroxylase, calcitonin gene-related peptide, and vasoactive intestinal peptide were also secretoneurin-immunoreactive, indicating a localization of secretoneurin in cholinergic, adrenergic, and sensory nerves. Lavage fluid levels of secretoneurin were increased at allergen exposure (p < 0.01-0.05). Levels of secretoneurin did not correlate with eosinophil cationic protein (rho = 0.1, p = 0.7). We conclude that secretoneurin has a widespread occurrence in nasal mucosal nerves of patients with seasonal allergic rhinitis and that increased nasal lavage fluid levels of secretoneurin may characterize ongoing allergen exposure. These data favor a role of secretoneurin in the local traffic of immune cells in human airway mucosa.

Adult↗

PubMed2002

Eosinophil infiltration and activation at the gastric ulcer margin in rats.

BACKGROUND: Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and behaviour of eosinophils during gastric ulcer healing. AIM: To examine the tissue infiltration and activation of eosinophils in the ulcer margin at different time points after ulcer induction (days 1-15). METHODS: Eosinophil peroxidase (EPO) staining and transmission electron microscopy (TEM) were used to observe eosinophil infiltration and activation in rats with acetic-acid-induced ulcer in the oxyntic mucosa. The distribution of macrophages was evaluated by immunocytochemistry using the macrophage-specific antibodies ED1 and ED2. RESULTS: There was a prominent increase in eosinophils around the ulcer margin at day 1 after ulcer induction, which peaked at day 5. TEM revealed characteristic signs of eosinophil activation, including cytolysis and piecemeal degranulation. Eosinophil cytolysis was the major form of activation, seen most frequently at day 5. A few scattered apoptotic eosinophils could also be observed. In normal controls and sham-operated rats, activated eosinophils were detected rarely. The distribution pattern of infiltrated eosinophils closely resembled that of macrophages at the ulcer margin. However, in the central part of the granulation tissue (at day 5) only macrophages could be found. CONCLUSIONS: There is marked infiltration and signs of activation of eosinophils together with macrophages at the margin of newly formed ulcers.

Animals↗

PubMed2002

NK cells and asthma.

NK cells have been associated with immune surveillance of tumor cells and defense mechanisms against various pathogens. However, by their capacity for immunoregulation NK cells may also play a role in determining the response to allergens. The novel possibility that NK cell activity may in part decide development of allergic airway inflammation and thus potentially be involved in the inception of asthma is discussed in this review article.

Asthma↗