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.
Scratching behavior was induced in 12 strains of mice and the frequency was compared. An injection of histamine at a dose of 50 nmol induced frequent scratching behavior only in ICR mice, although the same dose of serotonin induced frequent scratching behavior in all strains of mice except for A/J. Histamine (10 nmol), serotonin (1 nmol), substance P (50 nmol) and passive cutaneous anaphylaxis induced significant vascular permeability increase in BALB/c, ICR, ddY and NC/Nga mice. These four stimuli also induced frequent scratching behavior in ICR mice. However, they failed to induce substantial increase in the incidence of scratching in the other three strains, except for ddY, which exhibited a slight but significant increase against substance P injection. These results suggest that the ICR mouse is a good responder for scratching behavior against various stimuli, especially against histamine. Thus ICR mice may be suitable for studying mediators and/or mechanisms for itching.
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