Role of the Clotting System in Cell-Mediated Hypersensitivity

Abstract

Abstract Radioactive tracers and immunofluorescence were employed to detect and quantitate fibrinogen/fibrin deposition in two types of cell-mediated hypersensitivity reactions in the guinea pig. Classic delayed hypersensitivity (DH) reactions to Old Tuberculin and to the azobenzenearsonate hapten were characterized by a progressive increase in the fibrinogen (125I-HF) content which exceeded that of the albumin tracer (131I-HSA) and paralleled the development of induration and erythema. Accumulation of 125I-HF could be related both to increased vascular permeability to 125I-HF and, more specifically, to retarded efflux of extravascular 125I-HF from tuberculin reaction sites. Warfarin inhibited 125I-HF accumulation and the formation of urea-insoluble 125I-HF (cross-linked fibrin) as well as induration in tuberculin reactions. Immunofluorescence studies revealed the site of Fib deposition to be extravascular, among the connective tissue fibers of the dermis, similar to that in DH reactions in man. In contrast, little 125I-HF accumulated in cell-mediated reactions rich in basophils—cutaneous basophil hypersensitivity (CBH) reactions to keyhole limpet hemocyanin, ovalbumin, and dinitrochlorobenzene—due in part to less vascular leakage of macromolecules and to decreased formation of urea-insoluble fibrin. By immunofluorescence Fib deposits were found in CBH reactions in a pattern similar to that in DH reactions, but the intensity of staining was appreciably less. Thus, fibrin accumulation further distinguishes DH from CBH reactions and is very likely responsible for the induration characteristic of DH reactions.