Phenotypic changes of bone marrow-derived mast cells after intraperitoneal transfer into W/Wv mice that are genetically deficient in mast cells.

106

In certain models of allergic airway disease, mast cells facilitate the development of inflammation and airway hyper-responsiveness (AHR). To define the role of the high affinity IgE receptor (FcεRI) in the development of AHR, mice with a disruption of the α subunit of the high affinity IgE receptor (FcεRI−/−) were exposed on 10 consecutive days to nebulized OVA. Forty-eight hours after the last nebulization, airway responsiveness was monitored by the contractile response of tracheal smooth muscle to electrical field stimulation (EFS). After the 10-day OVA challenge protocol, wild-type mice demonstrated increased responsiveness to EFS, whereas similarly challenged FcεRI−/− mice showed a low response to EFS, similar to nonexposed animals. Further, allergen-challenged FcεRI−/− mice showed less airway inflammation, goblet cell hyperplasia, and lower levels of IL-13 in lung homogenates compared with the controls. IL-13-deficient mice failed to develop an increased response to EFS or goblet cell hyperplasia after the 10-day OVA challenge. We transferred bone marrow-derived mast cells from wild-type mice to FcεRI−/− mice 1 day before initiating the challenge protocol. After the 10-day OVA challenge, recipient FcεRI−/− mice demonstrated EFS-induced responses similar to those of challenged wild-type mice. Transferred mast cells could be detected in tracheal preparations. These results show that FcεRI is important for the development of AHR after an aerosolized allergen sensitization protocol and that this effect is mediated through FcεRI on mast cells and production of IL-13 in the lung.

Section: Discussionmentioning

confidence: 99%

Mast Cells, FcεRI, and IL-13 Are Required for Development of Airway Hyperresponsiveness after Aerosolized Allergen Exposure in the Absence of Adjuvant

Taube

Wei

Swasey

et al. 2004

106

“…Cultured MCs were generated as described (29). Cells from femora, adult spleens, or E14.5 fetal livers were cultured in aMEM-supplemented with 10% FBS and mouse Il3 (a gift from Dr. Sudo, Toray Industries, Kanagawa, Japan) at 50 U/ml in a humidified atmosphere of 5% CO 2 in the air at 37˚C.…”

Section: Preparation Of Cultured Mcsmentioning

confidence: 99%

A Notch Ligand, Delta-Like 1 Functions As an Adhesion Molecule for Mast Cells

Murata

Okuyama

Sakano

et al. 2010

Mast cells (MCs) accumulate in chronic inflammatory sites; however, it is not clear which adhesion molecules are involved in this process. Recently, the expression of Notch ligands was reported to be upregulated in inflammatory sites. Although Notch receptors are known as signaling molecules that can activate integrins, their contributions to the adhesion of MCs have not been studied. In this study, we demonstrated that mouse MCs efficiently adhered to stromal cells forced to express a Notch ligand, Delta-like 1 (Dll1). Surprisingly, the adhesion was a consequence of direct cell–cell interaction between MCs and Dll1-expressing stromal cells rather than activation of downstream effectors of Notch receptor(s)-Dll1. The adhesion of MCs to Dll1-expressing stromal cells remained even when the cell metabolism was arrested. The recognition was blocked only by inhibition of Notch receptor(s)–Dll1 interaction by addition of soluble DLL1, or mAbs against Dll1 or Notch2. Taken together, these results indicate that Notch receptor(s) and Dll1 directly promote the adhesion of MCs to stromal cells by acting as adhesion molecules. This appreciation that Notch receptor–ligand interactions have an adhesion function will provide an important clue to molecular basis of accumulation of MCs to inflammatory sites.

“…Peritoneal mast cells and macrophages were obtained from P. berghei ANKA-infected C57BL/6 mice at day 10 after the infection. Mast cells were collected from the peritoneal cavity of the mice by washing with Tyrode's buffer, and then peritoneal mast cells were isolated using 22.5% Nycodenz density gradients, according to the method previously reported (32). The isolated cells were washed with Tyrode's buffer three times.…”

Section: Tnf Production In Peritoneal Mast Cells and Macrophages In Vmentioning

confidence: 99%

Protective Roles of Mast Cells and Mast Cell-Derived TNF in Murine Malaria

Furuta¹,

Kikuchi²,

Iwakura

et al. 2006

TNF plays important roles in the protection and onset of malaria. Although mast cells are known as a source of TNF, little is known about the relationship between mast cells and pathogenesis of malaria. In this study, mast cell-deficient WBB6F1-W/Wv (W/Wv) and the control littermate WBB6F1+/+ (+/+) mice were infected with 1 × 105 of Plasmodium berghei ANKA. +/+ mice had lower parasitemia with higher TNF levels, as compared with W/Wv mice. Diminished resistance in W/Wv mice was considered to be due to mast cells and TNF. This fact was confirmed by experiments in W/Wv mice reconstituted with bone marrow-derived mast cells (BMMCs) of +/+ mice or of TNF−/− mice. W/Wv mice with BMMCs of +/+ mice exhibit lower parasitemia and mortality accompanying significantly higher TNF levels than those of W/Wv mice. Parasitemia in W/Wv mice with BMMCs of TNF−/− mice was higher than that in +/+ mice. Activation of mast cells by anti-IgE or compound 48/80 resulted in release of TNF and decrease of parasitemia. In addition, splenic hypertrophy and increased number of mast cells in the spleen were observed after infection in +/+ mice and W/Wv mice reconstituted with BMMCs of +/+ mice as compared with W/Wv mice. These findings propose a novel mechanism that mast cells and mast cell-derived TNF play protective roles in malaria.