These findings demonstrated that in this murine model airway eosinophilic inflammation is responsible for the development of airway remodeling as well as bronchial hyperresponsiveness in allergic bronchial asthma.

1 To evaluate the role of prostaglandin I 2 (PGI 2 ) in allergic in¯ammation, allergic responses in the airway, skin and T cells were studied in mice lacking the receptor for PGI 2 (the prostanoid IP receptor) through gene disruption. 2 Three inhalations of antigen caused an increase in plasma extravasation, leukocyte accumulation and cytokine (interleukin (IL)-4 and IL-5) production in the airway of sensitized mice. These airway in¯ammatory responses were signi®cantly greater in IP receptor de®cient mice than in wild-type mice.3 The vascular leakage caused by passive cutaneous anaphylaxis, substance P and 5-hydroxytryptamine was markedly increased in the skin of IP receptor de®cient mice, compared with comparably treated wild-type mice. 4 The inhalation of antigen in sensitized mice resulted in increased serum antigen speci®c IgE, total IgE and IgG levels. The magnitude of the elevations of each immunoglobulin level in IP receptor de®cient mice is notably higher than that in wild-type mice. To elucidate the mechanism of an enhancement of immunoglobulin production, the activity of T cells in sensitized and non-sensitized mice was studied by means of the production of cytokines. The antigen-induced IL-4 production by spleen cells from sensitized IP receptor de®cient mice was almost three times greater than that in wild-type mice. On the contrary, the anti-CD3 antibody-induced interferon-g production by CD4+ T cells from non-sensitized IP receptor de®cient mice was signi®cantly lower than that in wild-type mice. 5 The present data indicate that IP receptor de®ciency reinforced an allergic airway and skin in¯ammation by augmentation of vascular permeability increase and the T helper 2 cell function. These ®ndings suggest a regulatory role of PGI 2 in allergic in¯ammation.

The present findings demonstrated that epithelial changes following repeated allergen challenge are rapidly induced and recover after the cessation of exposure, but subepithelial fibrosis has a late onset and relatively irreversible changes, and subepithelial fibrosis in contrast to goblet cells hyperplasia did not appear to contribute to bronchial hyperresponsiveness, at least, in this mouse model.

1 Recently, much attention has been paid to the relationship between the nervous and immune systems. The present study was conducted to clarify the role of neurotrophin low anity receptor (p75N) in allergic airway in¯ammation and hyper-responsiveness (AHR) in mice by employing p75N gene de®cient mice. 2 Mice were immunized twice by intraperitoneal injections of ovalbumin (OA) at intervals of 12 days. OA was inhaled 10 days after the secondary immunization and repeated three times at 4 days interval. Twenty-four hours after the last inhalation, airway responsiveness to acetylcholine was measured and bronchoalveolar lavage¯uid (BALF) was obtained for examining the number of in¯ammatory cells and the level of cytokines. Serum immunoglobulin was measured as a marker of systemic immune response before the ®nal inhalation. 3 In wild-type mice, repeated antigen provocation resulted in airway eosinophilia, AHR and elevations in serum IgE and interleukin (IL)-4 and -5 in BALF. In p75N gene de®cient mice, none of the above parameters was observed after antigen provocation. The antigen-induced production of interferon (IFN)-g and nerve growth factor (NGF) were not altered by depletion of p75N gene. 4 The present ®ndings suggest that p75 gene de®ciency disrupt an allergic airway in¯ammation and AHR in mice by interfering type 2 helper T (Th2) cell responses.