Further Analysis of the Resistance of a Colony of Rats to Dextran

Abstract

Rats selectively bred for non-reactivity to ovomucoid and to clinical dextran (termed non-reactors) have a higher blood polymorphonuclear neutrophil count than do rats which react with an anaphylactoid reaction (termed reactors). This finding may explain why non-reactors do not exhibit the signs of arthritis when Freund’s adjuvant is injected into the hind paw. Nevertheless, the transfer of blood white cells and lymphocytes from spleen, thymus and lymph nodes of reactors fails to break down the resistance of non-reactors to dextran. Insulin likewise does not render non-reactor rats sensitive to dextran although it markedly potentiates the reaction in reactors. If new protein synthesis induced by insulin is involved in the potentiation, then non-reactors may lack the ability to synthesize this protein in the presence of insulin. However, insulin increases the severity of anaphylactic shock in both reactors and non-reactors when administered at the same time as the intravenous challenge of antigen.

Delayed Hypersensitivity Reactions in Rats and Their Response to Clinical Dextran

“…Later, West (1974) found that the lymph nodes of NR rats did not enlarge under such treatment whereas those of control Wistar rats (termed R rats) enlarged more than 20-fold during the development of arthritis. As adjuvantinduced arthritis resembles human rheumatoid arthri tis in many respects, the inability of NR rats to re spond to adjuvant is of clinical interest, particularly as the failure to respond to dextran was traced to an inherited autosomal recessive character .…”

Studies on Passive Transfer of Anti-Dextran and Anti-Egg Albumin Reactivity in the Rat

“…The differences also seem evident from previous descriptions of the respective reactions [9,14,21,24,25]. Possibly dextran acts predominently on intcgumental mast cells, and EA on visceral mast cells.…”

“…Goth [11] was unable to transfer reactivity against dextran to nonreactive rats by means of transfusions, and West [25] similarly failed to transfer sys temic anti-dextran reactivity by injecting blood or lymphoid cells. Apparently, the only experiments suggestive of antibody participation in a reaction similar to that in duced in normal rats by dextran were made by Polushkin [22].…”

“…Although evidence has been presented that hereditary traits may play an important role [23,25], suspicion has persisted that the reactions are immunologically deter mined. Even in the absence of known expo sure, immunization might have occurred through ingestion of the offending subst ance, or in some cases due to production of cross-reacting substances by bacteria [11], Many studies have failed to demonstrate an tibodies against the substances, but few defi nitive studies have been made.…”

Diet and Adjuvant-Induced Arthritis in the Rat

“…It has been suggested variously to be (a) a delayed hypersensitiv ity response to mycobacterial antigen; (b) an autoimmune disease in which the responsi ble antigen is either the mycobacterial frac tion combined with a tissue component or altered collagen, or (c) a local response of the tissues to the disseminated and indigesti ble adjuvant. The draining popliteal lymph nodes increased markedly in weight during the period of 20 days [6], starting even at day 5 to reach peak values of some 20 times those of controls by day 17 when usually ar thritic scores are also at their peak. Yet, withdrawal of added copper or magnesium or zinc (or all 3 trace metals together) from the diet results, in the present experiments, in arthritis failing to develop in these rats.…”