RESEARCH - Mast cell-derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice

[Guest guest]

J Allergy Clin Immunol. 2007 Jul;120(1):48-55. Epub 2007 May 7.

Mast cell-derived TNF contributes to airway hyperreactivity, inflammation,

and TH2 cytokine production in an asthma model in mice.

Nakae S, Ho LH, Yu M, Monteforte R, Iikura M, Suto H, Galli SJ.

Department of Pathology, Stanford University School of Medicine, Stanford,

CA 94305-5324, USA.

BACKGROUND: Mast cells, IgE, and TNF, which have been implicated in human

atopic asthma, contribute significantly to the allergic airway inflammation

induced by ovalbumin (OVA) challenge in mice sensitized with OVA without

alum. However, it is not clear to what extent mast cells represent a

significant source of TNF in this mouse model. OBJECTIVE: We investigated

the importance of mast cell-derived TNF in a mast cell-dependent model of

OVA-induced airway hyperreactivity (AHR) and allergic airway inflammation.

METHODS: Features of this model of airway inflammation were analyzed in

C57BL/6J-wild-type mice, mast cell-deficient C57BL/6J-Kit(W-sh)(/W-sh) mice,

and C57BL/6J Kit(W-sh/W-sh) mice that had been systemically engrafted with

bone marrow-derived cultured mast cells from C57BL/6J-wild-type or

C57BL/6J-TNF(-/-) mice. RESULTS: Ovalbumin-induced AHR and airway

inflammation were significantly reduced in mast cell-deficient

Kit(W-sh/W-sh) mice versus wild-type mice. By contrast, Kit(W-sh/W-sh) mice

that had been engrafted with wild-type but not with TNF(-/-) bone

marrow-derived cultured mast cells exhibited responses very similar to those

observed in wild-type mice. Mast cells and mast cell-derived TNF were not

required for induction of OVA-specific memory T cells in the sensitization

phase, but significantly enhanced lymphocyte recruitment and T(H)2 cytokine

production in the challenge phase. CONCLUSION: Mast cell-derived TNF

contributes significantly to the pathogenesis of mast cell-dependent and

IgE-dependent, OVA-induced allergic inflammation and AHR in mice, perhaps in

part by enhancing lymphocyte recruitment and T(H)2 cytokine production.

CLINICAL IMPLICATIONS: Our findings in mice support the hypothesis that mast

cell-derived TNF can promote allergic inflammation and AHR in asthma.

PMID: 17482668

http://www.ncbi.nlm.nih.gov/pubmed/17482668

Not an MD