Mast cell activation and migration to lymph nodes during induction of an immune response in mice.

Abstract

The mast cell response in skin and lymph nodes was examined during the sensitization phase of dinitrofluorobenzene (DNFB)-induced contact hypersensitivity in mice. Degranulation of 62% of mast cells in DNFB-exposed skin was evident within 30 min of a dual application of DNFB, reaching a peak of 77% at 24 h, and persisting in 42% after 5 d. Abundant expression of macrophage inflammatory protein (MIP)-1 ␣ and MIP-1 ␤ mRNAs and proteins was observed in keratinocytes, and mast cell degranulation was significantly inhibited after administration of neutralizing antibodies to MIP-1 ␣ , but not MIP-1 ␤ . During DNFB sensitization, the mast cell density in the skin decreased by half, concurrent with a fivefold expansion of mast cell numbers in draining lymph nodes. Fluorescent-labeled mast cells injected into the skin appeared in draining lymph nodes after application of DNFB, followed by subsequent migration to the spleen. In lymph nodes, mast cells were an abundant and predominant source of MIP-1 ␤ , neutralization of which partially inhibited T lymphocyte recruitment. These results indicate that mast cells contribute to the induction of this primary immune response by activation at and migration from the site of antigen encounter to draining lymph nodes, wherein they mediate T lymphocyte recruitment by production of MIP-1 ␤ . ( J. Clin. Invest. 1998. 102:1617-1626.)

Is there a role for mast cells in psoriasis?

“…In recent experiments with mice, mast cells and their TNF have been reported to enhance antigen-and Th17 celldependent development of a neutrophil-rich inXammatory response in airways [126] suggesting that mast cells can promote Th17 cell-dependent inXammation in vivo. In addition to local actions in the skin previous Wndings in mice show that as a result of dinitroXuorobenzene-induced contact hypersensitivity mast cells are activated and they migrate to draining lymph nodes wherein they can mediate T cell recruitment [198]. Further support for mast cellinduced lymph node activation and hypertrophy is provided by the study showing that activation of mast cells in mouse footpad by injection of Escherichia coli bacteria or compound 48/80 results in rapid draining of mast cell-derived preformed TNF to lymph nodes wherein it induces hypertrophy and recruitment of circulating T cells [115].…”

IL-15 induces mast cell migration via a pertussis toxin-sensitive receptor

“…Mice were killed by CO 2 asphyxiation and bone marrow aseptically flushed from femurs and tibias into complete RPMI-1640 media (10% heat-denatured FBS (56 C, 20 min), 100 U/mL penicillin, 100 lg/mL streptomycin, 30% WEHI-3b supernatant (as a source of murine IL-3) and 20% 3T3 supernatant (as a source of murine SCF) [51]) and maintained in a humidified chamber (5% CO 2 , 37 C).…”

Type 1 Diabetes in NOD Mice Unaffected by Mast Cell Deficiency

“…Akin to humans, in the universally used nonobese diabetic (NOD) mouse model of T1D, the highest genetic contributor to disease susceptibility maps to the major histocompatibility complex (21,22). In view of the T-cell dependency of this disease and the putative roles of mast cells in the control of T-cell responses, which may occur via direct antigen presentation to either CD4 + or CD8 + T cells (23)(24)(25), by induction of T-cell migration to lymph nodes (26,27), by control of dendritic cell activation and migration to lymph nodes (28)(29)(30)(31), or by control of the Th1 versus Th2 skewing (32)(33)(34)(35), it has been postulated that mast cells are likely important players in the development of T1D (14,15,36).…”