Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice

Abstract

BACKGROUND AND PURPOSEMast cell hyperplasia has been observed in the lungs of mice with experimental asthma, but few reports have studied basophils. Here, we attempted to discriminate and quantify mast cells and basophils in the lungs in a murine asthma model, determine if both cells were increased by multiple antigen challenges and assess the roles of those cells in asthmatic responses. EXPERIMENTAL APPROACHSensitized Balb/c mice were intratracheally challenged with ovalbumin four times. Mast cells and basophils in enzymatically digested lung tissue were detected by flow cytometry. An anti-FceRI monoclonal antibody, MAR-1, was i.p. administered during the multiple challenges. KEY RESULTSThe numbers of both mast cells (IgE + C-kit + ) and basophils (IgE + C-kit -CD49b + ) increased in the lungs after three challenges. Treatment with MAR-1 completely abolished the increases; however, a late-phase increase in specific airway resistance (sRaw), and airway eosinophilia and neutrophilia were not affected by the treatment, although the early-phase increase in sRaw was suppressed. MAR-1 reduced antigen-induced airway IL-4 production. Basophils infiltrating the lung clearly produced IL-4 after antigen stimulation in vitro; however, histamine and murine mast cell protease 1 were not increased in the serum after the challenge, indicating that mast cell activation was not evoked. CONCLUSION AND IMPLICATIONSBoth mast cells and basophils infiltrated the lungs by multiple intratracheal antigen challenges in sensitized mice. Neither mast cells nor basophils were involved in late-phase airway obstruction, although early-phase obstruction was mediated by basophils. Targeting basophils in asthma therapy may be useful for an early asthmatic response.

Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin‐induced allergic airway inflammation

“…Depletion of basophils with MAR‐1 may affect mast cells . To further confirm the key role of basophils in the Th2 immune response, adoptive transfer of basophils to naive BALB/c mice was performed.…”

Clinical view on the importance of dendritic cells in asthma

“…Antibodies secreted from plasma cells bind to the high affinity FcεRI on mast cells. On subsequent exposure to allergens, antibodies bound to FcεRI on mast cells cross-link causing a signal transduction leading to the activation of mast cells releasing pre-formed mediators from their granules together with many newly formed mediators [130,131]. Molecular signals to reduce the activation of mast cells can be promising to control inflammatory response.…”

Effect of Premedications in a Murine Model of Asparaginase Hypersensitivity

“…Unlike histamine and PAF, tryptase reaches peak concentrations ∼30-60 minutes after allergy onset, has a serum half-life of 90 minutes, and exhibits low serum concentrations in normal, nonallergic individuals (Laroche et al, 1991). Although other studies have suggested that histamine levels may be a more useful immediate (e.g., 10 minutes) indicator of the onset of allergies compared with the release of mast cell proteases in mice (Nabe et al, 2013), a biomarker of allergy that is elevated and stable for several hours after an allergic reaction may be more useful as an eventual clinical biomarker of asparaginase-induced allergies. Taken together, our results suggest that tryptase may be a possible clinical biomarker for confirming episodes of hypersensitivity to asparaginase.…”