A major contributory cause of arthritis in adjuvant-inoculated rats: Granulocytes
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Abstract
The predominant white cell-type in circulating blood of normal rats is the lymphocyte. Granulocytes increase in the circulating blood of adjuvant-inoculated rats; lymphocytes remain the same or increase slightly. Some drugs, like Cytosar® (cytarabine), inhibit granulocyte increases primarily and inhibit arthritis development completely. Pretreatment of normal rats with cytarbine also inhibits the local inflammation caused by direct injections ofM. butyricum into hidpaws of rats. Pre-treatment of rats withM. butyricum, causing granulocytes to increase in circulating blood, produces an exaggerated response to the subsequent inoculation ofM. butyricum directly into rats' paws.
Injection ofM. butyricum in non-arthritogenic vehicles (saline) does not produce the exaggerated response of granulocytes that occurs in response to injection in effective arthritogenic vehicles (mineral oil). Granulocytes are not increased greatly using the ineffective vehicle.
Finally, lysates of either rat white cells (granulocytes) or platelets, both of which increase in adjuvant-inoculated rats, produce striking inflammatory reactions when inoculated locally into rats' hindpaws. The addition of nonopsonizedM. butyricum to granulocytes obtained from adjuvant-inoculated rats causes a significant increase in the release of lysosomal enzymes.
From all these and other indirectly derived data, it is surmised that adjuvant inoculation produces a marked increase in granulocytes of circulating blood; as these increase with time, theM. butyricum molecules or some constituent derived from them (as determined by the distribution of tritiatedM. butyricum) arrive in joints and many other tissues, there reacting with granulocytes causing release of lysosomal constituents that produce the histopathology of adjuvant-disease. These result are discussed.
Keywords
Arthritis Inflammatory Reaction Cytarabine Direct Injection White CellPreview
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