¹²⁵I-Fibrin deposition in IgE-dependent immediate hypersensitivity reactions in mouse skin. Demonstration of the role of mast cells using genetically mast cell-deficient mice locally reconstituted with cultured mast cells

We investigated the clotting associated with IgE-dependent immediate hypersensitivity reactions in the mouse by injecting monoclonal mouse anti-dinitrophenyl IgE antibodies i.d. and, the next day, administering ¹²⁵I-guinea pig fibrinogen i.v. 10 to 30 min before i.v. antigen (2,4-dinitrophenylated human serum albumin) challenge. In normal mice, 2-hr passive cutaneous anaphylaxis (PCA) reactions were associated with substantial leakage of ¹²⁵I-fibrinogen and deposition of ¹²⁵I-fibrin. Thus, ears injected with IgE contained up to six times the total cpm of ¹²⁵I and up to 30 times the cross-linked ¹²⁵I-fibrin-associated cpm of ¹²⁵I than did control ears. Several lines of evidence indicated that the ¹²⁵I-fibrin deposition associated with the PCA reactions was dependent on the activity of mast cells: 1) Mast cell degranulation occurred at sites of PCA reactions. 2) Antigen-induced influx of ¹²⁵I-fibrinogen and deposition of ¹²⁵I-fibrin were virtually abolished by heating the IgE (56°C,, 1 hr) before i.d. injection. 3) Little or no IgE-dependent ¹²⁵I-fibrinogen influx or ¹²⁵I-fibrin deposition occurred in mast cell-deficient WBB6F₁-W/W(v) or WCB6F₁-S1/S1(d) mice. 4) Adoptive transfer of cutaneous mast cell populations into WBB6F₁-W/W(v) or WCB6F₁-S1-S1(d) mice. 4) Adoptive transfer of cutaneous mast cell populations into WBB6F₁-W/W(v) mice (by each of three approaches: i.v. transplantation of normal bone marrow cells or local i.d. injection of cultured, growth factor-dependent mast cells 2 days or 9 to 10 wk before antigen challenge) conferred on the recipients the ability to express the ¹²⁵I-fibrinogen influx and ¹²⁵I-fibrin deposition associated with PCA reactions. These data demonstrate that ¹²⁵I-fibrinogen influx and ¹²⁵I-fibrin deposition occurs in association with PCA reactions in the mouse, and that the reaction is largely or entirely dependent on the function of cutaneous mast cells. The experiments also demonstrate the utility of a novel model system for the analysis of mast cell function in vivo: WBB6F₁-W/W(v) mice locally reconstituted with mast cells by the injection of mast cell populations generated in vitro.