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Gut Microbes 2012Recently, we demonstrated a novel role for gastrointestinal mast cells (MCs) in the early events that lead to the generation of Th2 immunity to helminth infection. Mice... (Review)
Review
Recently, we demonstrated a novel role for gastrointestinal mast cells (MCs) in the early events that lead to the generation of Th2 immunity to helminth infection. Mice lacking MCs (Kit(W) /Kit(W-v) and Kit(W-Sh)) showed a significant inhibition of Th2 cell priming following infection with the parasitic helminth Heligmosomoides polygyrus bakeri (Hp). We showed that MCs degranulate during the early stages of infection when the helminth larvae invade the small intestinal tissue. Furthermore, MC degranulation was required for the enhanced expression and production of the tissue-derived cytokines IL-25, IL-33 and TSLP, which are required for the optimal orchestration and priming of type 2 immunity. In this addendum we aim to address several questions raised by our findings - in particular, the mechanisms through which MCs may recognize helminth exposure in the early stages of infection and by which they may enhance expression of critical tissue cytokines thus, enabling Th2 priming. Furthermore, we will discuss these findings in the context of recently described novel innate immune cells, such as type 2 hematopoietic progenitors and type 2 innate lymphoid cells.
Topics: Animals; Cell Degranulation; Cytokines; Mast Cells; Mice; Models, Biological; Nematospiroides dubius; Th2 Cells
PubMed: 22892692
DOI: 10.4161/gmic.21507 -
Scandinavian Journal of Immunology Jan 2008Activation of natural killer (NK) cells is induced via receptors like NKG2D, NKR-P1C and NKp46. This activation is balanced by interactions with inhibitory receptors. NK... (Comparative Study)
Comparative Study
Activation of natural killer (NK) cells is induced via receptors like NKG2D, NKR-P1C and NKp46. This activation is balanced by interactions with inhibitory receptors. NK cell activation can lead to cytotoxicity mediated via polarized exocytosis of secretory lysosomes (degranulation) and interferon (IFN)-gamma production. We studied cell surface mobilization of a molecule present in secretory lysosomes, CD107a (LAMP-1), to monitor the relationship between degranulation of NK cells and their production of IFN-gamma at the single cell level. A comparison of responses in naive mouse NK cells and NK cells pre-activated with the type I interferon-inducer tilorone demonstrated a dramatic influence of pre-activation, allowing potent degranulation and IFN-gamma responses to NKG2D mediated stimulation that were not observed with naive NK cells. Degranulation and IFN-gamma production were performed by overlapping NK cell populations with generally higher frequencies of degranulating than IFN-gamma producing NK cells. An NK cell subset analysis based on expression of Mac-1 and CD27 revealed that immature NK cells (Mac-1(lo) CD27(hi)) are preferentially degranulating, Mac-1(hi) CD27(hi) cells perform both effector functions efficiently, while the most mature (Mac-1(hi) CD27(lo)) NK cells display reduced degranulation but with maintained IFN-gamma production.
Topics: Animals; Antibodies, Monoclonal; Cell Degranulation; Cell Line, Tumor; Cells, Cultured; Coculture Techniques; Humans; Interferon-gamma; Killer Cells, Natural; Lymphocyte Activation; Lysosomal-Associated Membrane Protein 1; Mice; Mice, Inbred C57BL; NK Cell Lectin-Like Receptor Subfamily K; Receptors, Immunologic; Receptors, Natural Killer Cell
PubMed: 18028287
DOI: 10.1111/j.1365-3083.2007.02026.x -
The Journal of Clinical Investigation Apr 1994The strategic location of mast cells at the host-environment interface and their ability to release potent mediators of inflammation have suggested that these cells may...
The strategic location of mast cells at the host-environment interface and their ability to release potent mediators of inflammation have suggested that these cells may play a pivotal role in host defense against bacterial infection. The ability of the opportunistic pathogen, Escherichia coli, to induce degranulation of mast cells obtained from the mouse peritoneum was investigated. We determined that unlike a mutant derivative deficient in the FimH subunit of the fimbriae or nonfimbriated E. coli, type 1 fimbriated E. coli induced mast cell degranulation in vitro. The magnitude of mast cell degranulation was directly proportional to the number of adherent bacteria on the cell surface in the initial period of the interaction. Using a mouse model of bacterial peritonitis, we demonstrated mast cell degranulation and histamine release by type 1 fimbriated bacteria in vivo. Furthermore, beads coated with FimH but not with FimA, the major subunit of type 1 fimbriae, evoked mast cell release of histamine in vivo in amounts comparable to that elicited by type 1 fimbriated E. coli. These studies reveal that mast cells can be degranulated by interaction with type 1 fimbriated E. coli and that FimH, the mannose-binding component of the fimbriae, is a potent mast cell stimulant.
Topics: Adhesins, Escherichia coli; Animals; Bacterial Adhesion; Bacterial Proteins; Cell Degranulation; Escherichia coli; Fimbriae Proteins; Histamine Release; Male; Mast Cells; Mice; Mice, Inbred CBA
PubMed: 7512987
DOI: 10.1172/JCI117146 -
The European Respiratory Journal May 2002It was hypothesized that the distribution and activation of mast cells across the airway wall may reflect their function in asthma. The density of mast cells (intact and...
It was hypothesized that the distribution and activation of mast cells across the airway wall may reflect their function in asthma. The density of mast cells (intact and degranulated) within airway compartments in cartilaginous and membranous airways, obtained from autopsies on patients with fatal asthma, nonfatal asthma, and nonasthmatic control cases have been examined. In cartilaginous airways, the mean+/-SE density of mast cells in control cases was 27+/-9 cells x mm(-2). It was similar in nonfatal asthma (24+/-2 cells x mm(-2)) but reduced (p<0.05) in fatal asthma cases (16+/-2 cells x mm(-2)). In membranous airways, the density of mast cells in control cases was 155+/-21 cells x mm(-2) and was higher (p<0.05) in cases of nonfatal (270+/-51 cells x mm(-2)) and fatal asthma (219+/-26 cells x mm(-2)). Mast-cell density was greatest on the smooth muscle and mucous glands in cartilaginous airways and on the smooth muscle and outer airway wall in membranous airways. The percentage of degranulated mast cells was higher (p<0.05) in cases of asthma, related to disease severity, and was higher in cartilaginous than membranous airways. Degranulation was greatest on the smooth muscle in fatal asthma cases. Mast-cell distribution and degranulation varies between cartilaginous and membranous airways and across the airway wall. Degranulation of mast cells is related to asthma severity. The increased degranulation in proximal airways may reflect stimulation via the inhaled route.
Topics: Adolescent; Adult; Asthma; Cell Degranulation; Female; Humans; Male; Mast Cells; Middle Aged; Respiratory Mucosa
PubMed: 12030728
DOI: 10.1183/09031936.02.00275802 -
Journal of Pharmacological Methods May 1990Mast cells degranulation has been assessed by flow cytometry (FACS) taking advantage of the changes in the light scattering properties of mast cells stimulated by...
Mast cells degranulation has been assessed by flow cytometry (FACS) taking advantage of the changes in the light scattering properties of mast cells stimulated by secretagogues. In turn, these changes are based on the modification of size, shape, and granule content of the cells before and after stimulation. With FACS, it is possible to work with almost pure mast cell populations (greater than 99%). Moreover, responses to compound 48/80 are carried out in real time and on the same cell sample that acts as internal control. This technique is very sensitive as shown by the ED50 of compound 48/80 (0.051 micrograms/mL) compared to its ED50 on histamine release (0.131 micrograms/mL). The well-known inhibitory effect of disodium cromoglycate against compound 48/80 was clearly observed using FACS. Furthermore, FACS allowed to distinguish between specific degranulating effects and cytotoxicity. Among the secretagogues used, only the degranulation induced by phospholipase A2 was inhibited by in vivo treatment with dexamethasone. It is suggested that the inhibitory effect is due to induction of phospholipase A2-inhibitory proteins (lipocortins).
Topics: Animals; Cell Degranulation; Dexamethasone; Flow Cytometry; In Vitro Techniques; Mast Cells; Rats; Rats, Inbred Strains; Stimulation, Chemical
PubMed: 2329799
DOI: 10.1016/0160-5402(90)90062-p -
Methods (San Diego, Calif.) Sep 1997Mast cells are the primary effector cells of immediate hypersensitivity reactions in humans. Upon mast cell activation both preformed and newly synthesized mediators are...
Mast cells are the primary effector cells of immediate hypersensitivity reactions in humans. Upon mast cell activation both preformed and newly synthesized mediators are secreted. Histamine can be measured by fluorometric assays, radioenzymatic assays, and immunoassays. These methods have been applied to plasma and urine to detect histamine that had been released in vivo and to release histamine in vitro from basophils and mast cells. Another mast cell constituent is tryptase, which is a more selective marker of mast cells, because negligible amounts are found in basophils. beta-Tryptase is stored in secretory granules and is actively released when mast cells degranulate. alpha-Protryptase remains in the proenzyme form and is constitutively released from mast cells, and consequently its level in serum reflects total numbers of mast cells. alpha-Protryptase levels are elevated in serum at baseline in subjects with systemic mastocytosis, whereas beta-tryptase is elevated in serum from subjects with systemic anaphylaxis. These markers serve as precise clinical indicators of the involvement of mast cells in human disease.
Topics: Anaphylaxis; Basophils; Biomarkers; Cell Degranulation; Chymases; Histamine; Histamine Release; Humans; Hypersensitivity, Immediate; Infant; Mast Cells; Mastocytosis; Serine Endopeptidases; Sudden Infant Death; Tryptases
PubMed: 9281467
DOI: 10.1006/meth.1997.0494 -
The American Journal of Physiology May 1998We investigated the release of a stable contractile factor(s) from rabbit isolated polymorphonuclear leukocytes (PMNs; 10(8) cells/ml) incubated in Tyrode buffer at 37...
We investigated the release of a stable contractile factor(s) from rabbit isolated polymorphonuclear leukocytes (PMNs; 10(8) cells/ml) incubated in Tyrode buffer at 37 degrees C. PMNs were untreated, stimulated with N-formylmethionyl-leucyl-phenylalanine (FMLP; 0.1 microM), of degranulated with cytochalasin B (1 microM) in combination with FMLP (0.1 microM). Products from unstimulated PMNs incubated for 60 min caused significantly greater contraction of rabbit isolated aorta (0.56 +/- 0.12 g, n = 8) than did products released from PMNs during a 5-min incubation (0.32 +/- 0.07 g, n = 11, P < 0.05). Stimulation alone did not affect contractile factor release; however, products released from degranulated PMNs caused significantly greater aortic contraction (0.48 +/- 0.08 g, n = 5) than products from nondegranulated PMNs (0.24 +/- 0.04 g, n = 5, P < 0.05) after a 5-min incubation. The contractile activity of PMN-derived products was virtually abolished by heat (90 degrees C, 10 min) or protease (trypsin; 166 U/ml, 5 h) treatment. These findings suggest a PMN-derived protein vasoconstrictor(s) is spontaneously released at a slow rate in vitro and that degranulation can enhance this rate of release. Because PMN degranulation in vivo is associated with inflammation, these results support suggestions that PMN-derived contractile factors may contribute to the impaired blood flow observed during postischemic reperfusion.
Topics: Animals; Blood Proteins; Cell Degranulation; Cytochalasin B; Female; Male; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Rabbits; Vasoconstrictor Agents
PubMed: 9612362
DOI: 10.1152/ajpheart.1998.274.5.H1545 -
Cell and Tissue Research 1983To study the role of the prophenoloxidase activating system, an enzyme cascade located in the haemocytes of crustaceans, in the cellular defences of the freshwater...
To study the role of the prophenoloxidase activating system, an enzyme cascade located in the haemocytes of crustaceans, in the cellular defences of the freshwater crayfish, Astacus astacus in vitro, monolayer cultures of mixed or separated haemocyte populations, isolated by density gradient centrifugation, were challenged with the bacterium, Moraxella sp. pre-coated with phenoloxidase and the other attaching proteins in crayfish haemocyte lysate (HLS), or in the case of controls, with saline or Moraxella sp. pre-incubated in saline alone. Examination of the coverslips 1 h after inoculation revealed that, in the mixed haemocyte cultures, most of the cells had undergone profound degranulation and lysis following exposure to the HLS-coated bacteria. Cell lysis was also evident in the experimental semigranular cell monolayers, but not in the controls, although in those controls treated with the saline-incubated bacteria, the semigranular haemocytes had undergone degranulation without lysis. In contrast, the granular cells appeared to be unaffected by the saline-incubated Moraxella sp., and with the HLS-coated bacteria displayed only marked degranulation. Greater numbers of bacteria were always associated with the cells or cell remnants in the experimental cultures compared to the controls. We suggest that the attaching proteins of the prophenoloxidase cascade are strong nonself signals for the haemocytes, causing them to degranulate and release previously cell-bound recognition factors into the haemolymph, where they are free to trigger activation of adjacent haemocytes.
Topics: Animals; Astacoidea; Blood Cells; Catechol Oxidase; Cells, Cultured; Centrifugation, Density Gradient; Culture Media; Enzyme Precursors; Hemocytes; Microscopy, Phase-Contrast; Moraxella; Phagocytosis
PubMed: 6413069
DOI: 10.1007/BF00238297 -
Naunyn-Schmiedeberg's Archives of... 1980Phallolysin from Amanita phalloides (Vaill. ex Fr.) Secr., rubescenslysin from Amanita rubescens (Pers. ex Fr.) Gray, and fascicularelysin from Hypholoma fasciculare...
Phallolysin from Amanita phalloides (Vaill. ex Fr.) Secr., rubescenslysin from Amanita rubescens (Pers. ex Fr.) Gray, and fascicularelysin from Hypholoma fasciculare (Huds. ex Fr.) Kummer, in vitro caused disruption of mast cells in rat mesentery. The mast-cell-degranulating potency of rubenscenslysin and fascicularelysin roughly corresponded to their haemolytic potency; the dose-response curves were extremely steep and the cells were either completely destroyed or remained intact. The action of rubescenslysin and fascicularelysin was very fast: at 37 degrees C 95 resp. 90% of the cells were disrupted within 5 min. Phallolysin degranulated mast cells only at 10-50-fold haemolytic concentrations; the concentration-response curve was flatter, and the effect less radical: a high percentage of the cells underwent only incomplete degranulation. 75% of the cells were degranulated within 5 min. Fascicularelysin released marker molecules from both, lecithin and sphingomyelin liposomes.
Topics: Amanitins; Animals; Cytoplasmic Granules; Cytotoxins; Female; Fungal Proteins; In Vitro Techniques; Liposomes; Male; Mast Cells; Mycotoxins; Rats; Time Factors
PubMed: 7207644
DOI: 10.1007/BF00499259 -
Science (New York, N.Y.) Mar 1972Polymorphonuclear leukocytes are degranulated in the lumens of vessels in synovial membrane in humans with various types of inflammatory arthritis and in dogs with...
Polymorphonuclear leukocytes are degranulated in the lumens of vessels in synovial membrane in humans with various types of inflammatory arthritis and in dogs with synovitis induced by urate crystals. This degranulation, accompanied by the release of lysosomal enzymes and vasoactive materials, may be an important part of the mechanism resulting in vascular injury.
Topics: Animals; Arthritis; Cytoplasmic Granules; Dogs; Humans; Inclusion Bodies; Inflammation; Microscopy, Electron; Mitochondria; Neutrophils; Synovial Membrane; Synovitis; Time Factors; Uric Acid
PubMed: 4333994
DOI: 10.1126/science.175.4026.1139