Role of the clotting system in cell-mediated hypersensitivity. I. Fibrin deposition in delayed skin reactions in man.
The expression of delayed-type hypersensitivity in animals has been inhibited by a variety of anticoagulants, but direct evidence for activation of clotting in the evolution of these reactions has been lacking. Using the fluorescent antibody technique we here demonstrate that fibrin deposition is a prominent and consistent feature of both allergic contact dermatitis and classic delayed hypersensitivity skin reactions in man. Fib was detected in 55 of 58 delayed reactions studied at the peak of their intensity. The characteristic distribution of Fib-principally in the intervascular portions of the reticular dermis with sparing of vessels and their associated cuffs of mononuclear cells-is unusual and quite different from that described in antibody-mediated lesions in animals or man. Fib was found in vessel walls in only 2 of 94 biopsies studied. With a single exception, deposition of immunoglobulins and complement was not observed. The pathogensis and significance of Fib deposition in these reactions are not yet clear. Fib is ultimately derived from circulating fibrinogen, and its accumulation provides additional evidence for locally increased vascular permeability in delayed hypersensitivity. Polymerization of extravascular fibrinogen could be triggered nonspecifically by dermal elements (e.g., collagen) or by a product of sensitized lymphocytes. The appearance of Fib early in the development of these reactions (4-8 h after epicutaneous test with DNCB) and inhibition studies with anticoagulants together suggest that clotting may have a role in their pathogenesis, possibly by the release of bioactive peptides from fibrinogen/fibrin or by contributing to the induration characteristic of delayed hypersensitivity.
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D001777:Blood Coagulation; D003877:Dermatitis, Contact / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism*; D012882:Skin Tests
D005337:Fibrin