Non-IgE mediated mast cell activation

Yu, Yingxin; Blokhuis, Bart R.; Garssen, Johan; Redegeld, Frank A.

doi:10.1016/j.ejphar.2015.07.017

Cited by 151 publications

(107 citation statements)

References 133 publications

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“…SCF is an important growth factor for MC, but also induces chemotaxis and survival. 38 The importance of SCF in attracting MC into tumor environment was previously demonstrated by the migration of mouse primary MC toward mouse H22 hepatocarcinoma cells. 18 Surprisingly, HT29 colon cancer cells induced MC chemotaxis partly via the secretion of CCL15, while no SCF-induced migration was involved.…”

Section: Discussionmentioning

confidence: 97%

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Blokhuis

Derks

et al. 2018

OncoImmunology

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Chronic inflammation drives the development of colorectal cancer (CRC), where tumor-infiltrating immune cells interact with cancer cells in a dynamic crosstalk. Mast cells (MC), one of earliest recruited immune cells, accumulate in CRC tissues and their density is correlated with cancer progression. However, the exact contribution of MC in CRC and their interaction with colon cancer cells is poorly understood. Here, we investigated the impact of primary human MC and their mediators on colon cancer growth using 2D and 3D coculture models. Primary human MC were generated from peripheral CD34+ stem cells. Transwell chambers were used to analyze MC chemotaxis to colon cancer. Colon cancer cells HT29 and Caco2 differentially recruited MC by releasing CCL15 or SCF, respectively. Using BrdU proliferation assays, we demonstrated that MC can directly support colon cancer proliferation and this effect was mediated by their cellular crosstalk. 3D coculture models with cancer spheroids further confirmed the pro-tumor effect of MC on colon cancer growth, where direct cell-cell contact is dispensable and increased production of multiple soluble mediators was detected. Moreover, TLR2 stimulation of MC promoted stronger growth of colon cancer spheroids. By examining the transcriptome profile of colon cancer-cocultured MC versus control MC, we identified several MC marker genes, which were deregulated in expression. Our study provides an advanced in vitro model to investigate the role of human MC in cancer. Our data support the detrimental role of MC in CRC development and provide a molecular insight into the cellular crosstalk between MC and colon cancer cells.

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Section: Discussionmentioning

confidence: 97%

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Blokhuis

Derks

et al. 2018

OncoImmunology

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“…Most tissue cells can contribute to the innate response in an infected tissue. MCs express several PRRs and are capable of releasing proinflammatory mediators (54, 55). Several of these, including the potently immunostimulatory cytokine TNF, are stored in the MCs’ secretory granules and can be rapidly released upon activation of the MC (55).…”

Section: Discussionmentioning

confidence: 99%

Unimpaired Responses to Vaccination With Protein Antigen Plus Adjuvant in Mice With Kit-Independent Mast Cell Deficiency

et al. 2018

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Innate inflammatory responses are crucial for induction and regulation of T cell and antibody responses. Mast cell (MC)-deficient Kit mutant mice showed impaired adaptive immunity, suggesting that MCs provide essential adjuvant activities, and pharmacological MC activation was proposed as a new adjuvant principle. However, the Kit mutations result in complex alterations of the immune system in addition to MC deficiency. We revisited the role of MCs in vaccination responses using Mcpt5-Cre R26DTA/DTA and Cpa3Cre/+ mice that lack connective tissue MCs or all MCs, respectively, but feature an otherwise normal immune system. These animals showed no impairment of T and B cell responses to intradermal vaccination with protein antigen plus complete Freund’s adjuvant. Moreover, we demonstrate that the adjuvant effects of the MC secretagogue c48/80 in intradermal or mucosal immunization are independent of the presence of MCs. We hence find no evidence for a regulation by MCs of adaptive immune responses to protein antigens. The finding that immunological MC functions differ from those suggested by experiments in Kit mutants, emphasizes the importance of rigorous tests in Kit-independent MC-deficiency models.

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“…This property contributes to G protein-activation. The activated G proteins can produce exocytosis from mast cells, the synthesis of phosphatidylinositol 3-kinase, and the formation of arachidonate metabolites [31,37]. The stimulus of phosphatidylinositol 3-kinase activates phospholipase C gamma, which in turn invokes the hydrolysis of phosphatidylinositol 4,5-bisphosphate generating inositol 1,4,5-trisphosphate and diacylglycero.…”

Section: Mechanisms Of Pseudoallergymentioning

confidence: 99%

“…In non-IgE-mediated anaphylactoid reactions, various components (IgG, complement components, neuropeptides, cytokines, chemokines, and other inflammatory products) [26,27,28,29,30] directly stimulate the degranulation of mast cells and the selective release of mediators. Besides these endogenous stimuli, some exogenous molecules, which cause drug side effects can also directly activate mast cells [31], such as a vitamin K 1 injection or a Qingkailing injection [32,33]. Different from IgE-mediated allergy, which is mediated by cell-surface receptors, the drugs are able to induce mast cell degranulation and alter enzymatic activity through various pathways [34,35].…”

Section: Mechanisms Of Pseudoallergymentioning

confidence: 99%

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Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

Zhang

Li²,

Shi³

et al. 2017

Pharmacology

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Adverse drug reactions occur frequently and can trigger pseudoallergy, which has become a serious threat to public health. Pseudoallergy is a typical non-immune anaphylactic reaction characterized by the independence of antigen-specific immune responses. In the clinic, pseudoallergy is often elicited by the first dose of medication, and here lies its unpredictability and occasional lethal outcome. However, the mechanisms of pseudoallergy are not well understood. This review focusses on the causes and mechanisms of pseudoallergy induced by drugs. Two categories of mechanisms will be considered, namely, (1) complement activation-related pseudoallergy and (2) mast cell activation-related pseudoallergy. The factors that induce pseudoallergy include opioid drugs, complement activation-related pseudoallergenic drugs, nonsteroidal anti-inflammatory drugs and traditional Chinese medicine injections.

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Non-IgE mediated mast cell activation

Cited by 151 publications

References 133 publications

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Unimpaired Responses to Vaccination With Protein Antigen Plus Adjuvant in Mice With Kit-Independent Mast Cell Deficiency

Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

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