The Mast Cell in Innate and Adaptive Immunity

Shelburne, Christopher P.; Abraham, Soman N.

doi:10.1007/978-1-4419-9533-9_10

Cited by 65 publications

(55 citation statements)

References 217 publications

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“…However, recent data clearly document their important protective roles in innate host defenses against parasites, bacteria, and even arthropod and reptile toxins (2)(3)(4)(5). Indeed, by responding to a wide spectrum of stimuli and releasing multiple biologically active substances, mast cells can initiate innate responses, which in turn contribute to the resolution of infection and to resistance to envenomation.…”

mentioning

confidence: 99%

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Azouz

Zur

Efergan

et al. 2014

The Journal of Immunology

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Secretion of inflammatory mediators prestored in mast cells secretory granules (SGs) enhances immune responses such as in allergy and host defense. However, the mechanisms underlying the biogenesis of the SGs remain largely unresolved. By combining high-resolution live cell imaging and quantitative morphometric analyses, we show that the small GTPase Rab5 controls the SG size and cargo composition by a VAMP8-dependent fusion mechanism. Knockdown of the endogenous Rab5, or expression of constitutively negative mutants, significantly reduces the size of SGs and increases their number. Conversely, expression of constitutively active Rab5 mutants induces few, but giant, SGs. Both the small and giant SGs maintain their exocytosis competence. Finally, we show that Rab5-mediated fusion between Golgi-derived SGs and early endosomes precedes the maturation of the SGs, as reflected by the recruitment of Rab27B, and allows the incorporation of cargo, such as CD63, that traffics through endosomes. Collectively, our results assign Rab5 a key role in mediating mast cell SG fusion during biogenesis, thereby controlling the amount and composition of the SGs content and maintaining the communication between new and pre-existing SGs.

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mentioning

confidence: 99%

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Azouz

Zur

Efergan

et al. 2014

The Journal of Immunology

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“…7 Mast cells are bone marrow-derived hematopoietic cells that are preferentially located in tissues exposed to the environment, such as skin, airways, and gastrointestinal tract. 8,9 Because of this location, they are one of the first immune cells to interact with invading pathogens or antigens. After activation, mast cells exert their biologic functions by releasing preformed as well as de novo synthesized mediators including histamine, proteases, numerous cytokines, and chemokines.…”

Section: Introductionmentioning

confidence: 99%

Mast cells play a protumorigenic role in primary cutaneous lymphoma

Rabenhorst

Schlaak

Heukamp

et al. 2012

Blood

117

104

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AbstractPrimary cutaneous lymphomas (PCLs) are clonal T- or B-cell neoplasms, which originate in the skin. In recent years, mast cells were described as regulators of the tumor microenvironment in different human malignancies. Here, we investigated the role of mast cells in the tumor microenvironment of PCL. We found significantly increased numbers of mast cells in skin biopsies from patients with cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL). Mast cell infiltration was particularly prominent in the periphery, at lymphoma rims. Interestingly, CTCL and CBCL patients with a progressive course showed higher mast cell counts than stable patients, and mast cell numbers in different stages of CTCL correlated positively with disease progression. In addition, mast cell numbers positively correlated with microvessel density. Incubating primary CTCL cells with mast cell supernatant, we observed enhanced proliferation and production of cytokines. In line with our in vitro experiments, in a mouse model of cutaneous lymphoma, tumor growth in mast cell–deficient transgenic mice was significantly decreased. Taken together, these experiments show that mast cells play a protumorigenic role in CTCL and CBCL. Our data provide a rationale for exploiting tumor-associated mast cells as a prognostic marker and therapeutic target in PCL.

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“…Mast cells are also activated, independently of IgE, by neuropeptides , toxins (Depinay et al, 2006), bacterial and viral antigens (Abel et al, 2011;Avila and Gonzalez-Espinosa, 2011), immune cells (Mekori and Metcalfe, 1999;Minai-Fleminger et al, 2010), as well as by many of their own secreted mediators, which further amplify the inflammatory response (Gilfillan et al, 2009;Rudich et al, 2012). While these inflammatory responses are recognized as allergy in hypersensitive individuals, physiologically, they mediate mast cell functions in innate and adaptive immunity (Shelburne and Abraham, 2011;Tsai et al, 2011).…”

Section: Mast Cellsmentioning

confidence: 99%