scholarly journals Human mast cells synthesize new granules during recovery from degranulation. In vitro studies with mast cells purified from human lungs

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 76-85
Author(s):  
AM Dvorak ◽  
RP Schleimer ◽  
LM Lichtenstein
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Human Lung ◽  
Immunoglobulin E ◽  
Release Kinetics ◽  
Recovery Period ◽  
Human Mast Cell ◽  
Secretory Cells ◽  
Early Recovery ◽  
Cytoplasmic Granules

Secretory cells undergoing release and recovery events related to constitutive and/or stimulus-initiated secretion might be expected to undergo distinctive changes in morphology as well. We studied the release and recovery events of human mast cell secretion stimulated by antibody to immunoglobulin E. We used enzymatically digested mast cells from human lung specimens further purified by countercurrent centrifugation elutriation. Release kinetics were like those reported for isolated human lung mast cells. In two complete kinetic experiments we restudied these early release patterns (0 to 30 minutes). Mast cells, either stimulated or controls, were then cultured and sampled for electronmicroscopic studies at periodic intervals (3 to 48 hours). We describe events of the late recovery period here, although some overlap with processes seen in early recovery samples occurred. Mast cells that released nearly all their cytoplasmic granules and exteriorized the containers, eg, granule-channel membranes, underwent progressive enlargement of Golgi structures and development of numerous small cytoplasmic vesicles and small, membrane-bound granules filled with particulate and dense content. Ultimately, new mature cytoplasmic granules of all substructural patterns occurred. Nuclear blast changes and expansion of cytoplasmic mass accompanied this period of new granule synthesis. Mixed recovery patterns were present in individual cells. These represented the morphological expression of a variety of recovery events. Thus, some cells showed a combination of channel recovery and remodeling to form new granule containers within which condensation of content produced crystalline patterns, as well as synthesis of new granules, as described here. This morphological versatility resulted in multiple mast cell morphological phenotypes during these release and recovery processes.

scholarly journals Human mast cells synthesize new granules during recovery from degranulation. In vitro studies with mast cells purified from human lungs

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 76-85 ◽  
Author(s):  
AM Dvorak ◽  
RP Schleimer ◽  
LM Lichtenstein
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Human Lung ◽  
Immunoglobulin E ◽  
Release Kinetics ◽  
Recovery Period ◽  
Human Mast Cell ◽  
Secretory Cells ◽  
Early Recovery ◽  
Cytoplasmic Granules

Abstract Secretory cells undergoing release and recovery events related to constitutive and/or stimulus-initiated secretion might be expected to undergo distinctive changes in morphology as well. We studied the release and recovery events of human mast cell secretion stimulated by antibody to immunoglobulin E. We used enzymatically digested mast cells from human lung specimens further purified by countercurrent centrifugation elutriation. Release kinetics were like those reported for isolated human lung mast cells. In two complete kinetic experiments we restudied these early release patterns (0 to 30 minutes). Mast cells, either stimulated or controls, were then cultured and sampled for electronmicroscopic studies at periodic intervals (3 to 48 hours). We describe events of the late recovery period here, although some overlap with processes seen in early recovery samples occurred. Mast cells that released nearly all their cytoplasmic granules and exteriorized the containers, eg, granule-channel membranes, underwent progressive enlargement of Golgi structures and development of numerous small cytoplasmic vesicles and small, membrane-bound granules filled with particulate and dense content. Ultimately, new mature cytoplasmic granules of all substructural patterns occurred. Nuclear blast changes and expansion of cytoplasmic mass accompanied this period of new granule synthesis. Mixed recovery patterns were present in individual cells. These represented the morphological expression of a variety of recovery events. Thus, some cells showed a combination of channel recovery and remodeling to form new granule containers within which condensation of content produced crystalline patterns, as well as synthesis of new granules, as described here. This morphological versatility resulted in multiple mast cell morphological phenotypes during these release and recovery processes.

Mast Cell Heterogeneity in Human Lung Tissue

1989 ◽  
Vol 77 (3) ◽  
pp. 297-304 ◽  
Author(s):  
F. J. Van Overveld ◽  
L. A. M. J. Houben ◽  
F. E. M. Schmitz du Moulin ◽  
P. L. B. Bruijnzeel ◽  
J. A. M. Raaijmakers ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Alcian Blue ◽  
Lung Tissue ◽  
Human Lung ◽  
Immunoglobulin E ◽  
Prostaglandin D2 ◽  
Leukotriene C4 ◽  
Human Lung Tissue ◽  
No Release

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

scholarly journals Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction

2018 ◽  
Vol 19 (12) ◽  
pp. 4092 ◽  
Author(s):  
Chen Shao ◽  
Bingjie Fu ◽  
Ning Ji ◽  
Shunli Pan ◽  
Xiaoxia Zhao ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Allergic Reaction ◽  
Nuclear Factor Kappa B ◽  
Immunoglobulin E ◽  
Mast Cell Activation ◽  
Human Mast Cell ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.

scholarly journals Roles of IgE and Histamine in Mast Cell Maturation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2170
Author(s):  
Satoshi Tanaka ◽  
Kazuyuki Furuta
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Cell Maturation ◽  
Tissue Type ◽  
Human Mast Cell ◽  
Therapeutic Effects ◽  
Serum Ige ◽  
Cell Functions ◽  
Histamine Synthesis

Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fcε receptor I (FcεRI), a high affinity receptor of IgE, were found to be positively regulated by IgE. IgE could protect murine cultured mast cells from apoptotic cell death induced by the deprivation of interleukin-3 and a certain kind of IgE could activate immature mast cells in the absence of antigens, leading to the release of pro-inflammatory cytokines and a transient increase in histamine synthesis. Histamine synthesis in mast cells was found to be required for the maturation of murine connective tissue-type mast cells, raising the possibility that IgE indirectly modulates local mast cell maturation. Although it remains controversial to what extent this concept of “monomeric IgE effects” could have relevance in the modulation of human mast cell functions, the therapeutic effects of anti-IgE antibodies might be accounted for in terms of the decreased serum IgE concentrations. Because drastic increases in serum IgE concentrations are often observed in patients with atopic dermatitis and chronic urticaria, a close investigation of the roles of IgE in mast cell maturation should contribute to development of novel therapeutic approaches for these inflammatory diseases.

scholarly journals Essential roles of sphingosine-1–phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema

2010 ◽  
Vol 207 (3) ◽  
pp. 465-474 ◽  
Author(s):  
Carole A. Oskeritzian ◽  
Megan M. Price ◽  
Nitai C. Hait ◽  
Dmitri Kapitonov ◽  
Yves T. Falanga ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Pulmonary Edema ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Mast Cell Activation ◽  
Human Mast Cell ◽  
Cell Functions ◽  
Sphingosine 1 Phosphate

Systemic exacerbation of allergic responses, in which mast cells play a critical role, results in life-threatening anaphylactic shock. Sphingosine-1–phosphate (S1P), a ligand for a family of G protein–coupled receptors, is a new addition to the repertoire of bioactive lipids secreted by activated mast cells. Yet little is known of its role in human mast cell functions and in anaphylaxis. We show that S1P2 receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release. Immunoglobulin E–triggered anaphylactic responses, including elevation of circulating histamine and associated pulmonary edema in mice, were significantly attenuated by the S1P2 antagonist JTE-013 and in S1P2-deficient mice, in contrast to anaphylaxis induced by administration of histamine or platelet-activating factor. Hence, S1P and S1P2 on mast cells are determinants of systemic anaphylaxis and associated pulmonary edema and might be beneficial targets for anaphylaxis attenuation and prophylaxis.

scholarly journals Differences in the behavior of cytoplasmic granules and lipid bodies during human lung mast cell degranulation.

1984 ◽  
Vol 99 (5) ◽  
pp. 1678-1687 ◽  
Author(s):  
A M Dvorak ◽  
I Hammel ◽  
E S Schulman ◽  
S P Peters ◽  
D W MacGlashan ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Human Lung ◽  
Specific Antigen ◽  
Mast Cell Degranulation ◽  
Mast Cell Activation ◽  
Lipid Bodies ◽  
Cytoplasmic Granules ◽  
Lung Mast Cell

We used a morphometric and autoradiographic approach to analyze changes in specific cytoplasmic granules and cytoplasmic lipid bodies associated with human lung mast cell degranulation. Mast cells were dissociated from lung tissue by enzymatic digestion and were then enriched to purities of up to 99% by countercurrent centrifugation elutriation and recovery from columns containing specific antigen bound to Sepharose 6 MB. Degranulation was induced by goat anti-IgE. At various intervals after stimulation, parallel aliquots of cells were recovered for determination of histamine release or were fixed for transmission electron microscopy. We found that lipid bodies, electron-dense structures that lack unit membranes, were present in both control and stimulated mast cells. Autoradiographic analysis showed that lipid bodies represented the major repository of 3H-label derived from [3H]arachidonic acid taken up from the external milieu. By contrast, the specific cytoplasmic granules contained no detectable 3H-label. In addition, lipid bodies occurred in intimate association with degranulation channels during mast cell activation, but the total volume of lipid bodies did not change during the 20 min after stimulation with anti-IgE. This result stands in striking contrast to the behavior of specific cytoplasmic granules, the great majority of which (77% according to aggregate volume) exhibited ultrastructural alterations during the first 20 min of mast cell activation. These observations establish that mast cell cytoplasmic granules and cytoplasmic lipid bodies are distinct organelles that differ in ultrastructure, biochemistry, and behavior during mast cell activation.

scholarly journals Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ofir Klein ◽  
Ronit Sagi-Eisenberg
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Molecular Mechanisms ◽  
Secretory Granules ◽  
Cell Types ◽  
Secretory Cells ◽  
Regulated Exocytosis ◽  
Open Questions ◽  
Conflicting Evidence ◽  
Compound Exocytosis

Anaphylaxis is a notorious type 2 immune response which may result in a systemic response and lead to death. A precondition for the unfolding of the anaphylactic shock is the secretion of inflammatory mediators from mast cells in response to an allergen, mostly through activation of the cells via the IgE-dependent pathway. While mast cells are specialized secretory cells that can secrete through a variety of exocytic modes, the most predominant mode exerted by the mast cell during anaphylaxis is compound exocytosis—a specialized form of regulated exocytosis where secretory granules fuse to one another. Here, we review the modes of regulated exocytosis in the mast cell and focus on compound exocytosis. We review historical landmarks in the research of compound exocytosis in mast cells and the methods available for investigating compound exocytosis. We also review the molecular mechanisms reported to underlie compound exocytosis in mast cells and expand further with reviewing key findings from other cell types. Finally, we discuss the possible reasons for the mast cell to utilize compound exocytosis during anaphylaxis, the conflicting evidence in different mast cell models, and the open questions in the field which remain to be answered.

scholarly journals The transcriptional program, functional heterogeneity, and clinical targeting of mast cells

2017 ◽  
Vol 214 (9) ◽  
pp. 2491-2506 ◽  
Author(s):  
Gökhan Cildir ◽  
Harshita Pant ◽  
Angel F. Lopez ◽  
Vinay Tergaonkar
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Small Population ◽  
Transcriptional Program ◽  
Cell Functions ◽  
New Concepts ◽  
Health And Disease ◽  
Ige Mediated

Mast cells are unique tissue-resident immune cells that express an array of receptors that can be activated by several extracellular cues, including antigen–immunoglobulin E (IgE) complexes, bacteria, viruses, cytokines, hormones, peptides, and drugs. Mast cells constitute a small population in tissues, but their extraordinary ability to respond rapidly by releasing granule-stored and newly made mediators underpins their importance in health and disease. In this review, we document the biology of mast cells and introduce new concepts and opinions regarding their role in human diseases beyond IgE-mediated allergic responses and antiparasitic functions. We bring to light recent discoveries and developments in mast cell research, including regulation of mast cell functions, differentiation, survival, and novel mouse models. Finally, we highlight the current and future opportunities for therapeutic intervention of mast cell functions in inflammatory diseases.

Immunologic mast cell-mediated responses and histamine release are attenuated by heparin

1992 ◽  
Vol 73 (3) ◽  
pp. 1093-1101 ◽  
Author(s):  
J. Lucio ◽  
J. D'Brot ◽  
C. B. Guo ◽  
W. M. Abraham ◽  
L. M. Lichtenstein ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Immunoglobulin E ◽  
Specific Antigen ◽  
Calcium Ionophore ◽  
Intradermal Injection ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Dependent Manner

Heparin has been shown to act as a competitive inhibitor of inositol 1,4,5-triphosphate (InsP3) receptors in various cell types. Because InsP3 is one of the second messengers involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit mast cell-mediated reactions. Therefore, in allergic sheep, we tested this hypothesis in two mast cell-mediated reactions induced by immunologic and nonimmunologic stimuli: immediate cutaneous reaction (ICR) and acute bronchoconstrictor response (ABR). In 12 sheep allergic to Ascaris suum antigen, the surface area of the skin wheal was determined 20 min after intradermal injection (0.05 ml) of increasing concentrations of specific antigen, compound 48/80, and histamine, without and after pretreatment with heparin (100, 300, or 1,000 U/kg i.v.). Antigen, compound 48/80, and histamine produced concentration-dependent increases in ICR. Heparin “partially” inhibited the ICR to antigen and compound 48/80 in a dose-dependent manner without modifying the ICR to histamine. The heparin preservative benzyl alcohol was ineffective. In 11 additional sheep, specific lung resistance was measured before and after inhalation challenges with antigen, compound 48/80, and histamine without and with aerosol heparin pretreatment (1,000 U/kg). Heparin blocked the antigen- and compound 48/80-induced bronchoconstriction without modifying the airway effects of histamine. In isolated human uterine mast cells, heparin inhibited the anti-immunoglobulin E- but not the calcium ionophore- (A23187) induced histamine release. These data suggest that heparin inhibits the ICR and ABR induced by stimuli that produce immunologic and nonimmunologic mast cell degranulation without attenuating the effects of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Selective Early Production of CCL20, or Macrophage Inflammatory Protein 3α, by Human Mast Cells in Response to Pseudomonas aeruginosa

2003 ◽  
Vol 71 (1) ◽  
pp. 365-373 ◽  
Author(s):  
Tong-Jun Lin ◽  
Lauren H. Maher ◽  
Kaede Gomi ◽  
Jeffrey D. McCurdy ◽  
Rafael Garduno ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Mast Cells ◽  
Immune Responses ◽  
Immunoglobulin E ◽  
Calcium Ionophore ◽  
Human Mast Cell ◽  
Gm Csf ◽  
Human Mast Cells ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

ABSTRACT Mast cells are important as sentinel cells in host defense against bacterial infection. Much of their effectiveness depends upon recruiting other immune cells; however, little is known about the mechanisms of this response. CCL20, also known as macrophage inflammatory protein-3α (MIP-3α), Exodus, and LARC, is a chemokine known to be a potent chemoattractant for immature dendritic cells and T cells. In this study, we examined the human mast cell production of both CCL20 and granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical cytokine for innate immune responses in the lung, in response to Pseudomonas aeruginosa. Reverse transcription-PCR and Western blot analysis demonstrated that the human mast cells (HMC-1) express CCL20 mRNA and are able to produce a significant amount (32.4 ng/ml) of CCL20 protein following stimulation by calcium ionophore and phorbol myristate acetate. Importantly, P. aeruginosa potently stimulated CCL20 production in human cord blood-derived mast cells (CBMC), with production peaking at 6 h after stimulation. This time course of expression was distinct from that of GM-CSF, which peaked after 24 to 48 h. Significant CCL20 production did not occur following immunoglobulin E-mediated activation of CBMC under conditions which induced a substantial GM-CSF response. Interestingly, the CCL20 response of mast cells to P. aeruginosa was relatively resistant to inhibition by the corticosteroid dexamethasone, interleukin-10, or cyclosporine, while GM-CSF production was potently inhibited. However, P. aeruginosa-induced CCL20 production was blocked by the protein kinase C (PKC) inhibitor Ro 31-8220 and a PKC pseudosubstrate. These results support a role for human mast cells in the initiation of immune responses to P. aeruginosa infection.

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