Injury And Inflammation Induced In The Microcirculation Of The Rabbit By Antigen-Antibody Complexes

Abstract

An experimental model was used to study the morphogenesis, quantitation and kinetics of the inflammatory response in the dermis of rabbits. New Zealand White rabbits were immunized with ovalbumin, bled, the antibody precipitated by ammonium sulphate and redissolved in saline. Circulating antibody was determined by the quantitative precipitin test. The reversed passive Arthus reaction was elicited by injecting normal rabbits intravenously with antigen [1.0 gm] and intradermally with 0.9 mg of antibody, in triplicate sites. The lesions were allowed to develop for 1-8, 18 and 24 hours post-injection. To assess the inflammatory response, 5 parameters were examined: 1) Exudation of plasma using 125I-serum albumin; 2) Infiltration of leukocytes with 51Cr-labelled cells; 3) Hemorrhage with 59Fe-erythrocytes; 4) Formation of microthrombi with 111In-platelets; and 5) Blood flow with 57Co-microspheres. The animals were killed, the lesions punched out with a cork borer and counted in a gamma spectrometer. Skin lesions from rabbits not injected with tracers were fixed in glutaraldehyde-formalin and prepared for microscopic examination. With the aid of these techniques, increase of vascular permeability and the formation of microthrombi peaked in 2-hour old lesions. Increased blood flow peaked in leasions 3-4 hours postinjection. Infiltration of polymorphonuclear leukocytes reached a maximum in lesions 2-3 hours old, followed by hemorrhage, which reached a maximum and plateaued after 4 hours. Immune complexes may induce a hemorrhagic inflammation, the kinetics of which can be ascertained. Preliminary studies indicate that these techniques are applicable for the examination of experimentally-induced hypersensitivity pneumonitides and disorders of the pulmonary microcirculation.