The kinetics and appearance of extracellular phospholipase A2 (PLA2) activity and its relationship to the appearance of arachidonic acid (AA) metabolites in the peritoneal cavity of mice injected with zymosan is described. AA metabolites levels including leukotriene C4 (LTC4) were maximum 15-30 min after zymosan. Peak PLA2 activity was also found 15-30 min after zymosan and was significantly increased above levels found in saline control exudates (3.83 +/- 0.89 and 0.35 +/- 0.11, respectively, p less than or equal to 0.05). Results show that an extracellular PLA2 is present in zymosan peritonitis.
A radioisotopic method, originally developed for measuring the cellular response in delayed hypersensitivity lesions in mice, has been evaluated in adjuvant arthritic rats. Focal accumulation of 5-iodo-2'-de~xyuridine-'~'I (""IUdR) at a site of antigen challenge (left pinna) was measured and expressed as increased radioactivity in the challenged (left) over the unchallenged (right) ear (L/R ear ratio). Immunologic specificity of the assay was established with anti-lymphocyte globulin (ALG)-treated arthritic rats. ALG significantly inhibited the "'IUdR L/R ear ratio; normal rabbit globulin had no effect on this parameter. A significant negative correlation was observed between the "'IUdR ear ratios and subjective arthritic scores in established adjuvant disease. Certain characteristics of the " W d R radiometric ear assay in rats were established in several types of experiments: disappearance of the isotope from blood, whole body irradiation studies in turpentine-injected rats, and cyclophosphamide pretreatment in a sheep erythrocyte antigenic system. The results of this study support the utility of the "'IUdR ear assay to quantify cellular accumulation at a site of antigen challenge in adjuvant arthritic rats and possibly other antigenic systems in this species.It is well established that intradermal administration of either Mycobacteria tuberculosis or Myco- Submitted for publication December 28, 1979; accepted February 21, 1980. bacteria butyricum ( M butyricum) in mineral oil into the hindlimb of rats induces an arthropathy known as adjuvant arthritis, with features that resemble rheumatoid arthritis and Reiter's disease in humans (1,2). Although the mechanisms involved in adjuvant arthritis induction have not been elucidated, there is some evidence that the syndrome represents a form of cellular hypersensitivity. This conclusion is based on the fact that swelling occurs in noninjected hindlimbs 10 to 14 days after antigen sensitization, and that the disease can be passively transferred to naive rats of the same inbred strain by means of intact lymphoid cells (3-6).Classically, inflammation is evaluated in vivo by indirect means, such as scoring induration and erythema, and measurement of increases in ear or footpad thickness. Skin reactivity to an antigen challenge is difficult to quantify in the rat, and therefore has not been generally used to measure delayed type hypersensitivity (DTH) in this species. Although measurements of swelling or erythema may also reflect the degree of a DTH response, they do not permit discrimination between the nonspecific inflammation and the cellular component of the response.Several more objective methods have been described for the measurement of delayed hypersensitivity (7-lo), and one technique that allows discrimination between cellular response and nonspecific inflammation under defined conditions is the method developed and characterized in the mouse by Vadas et a1 (10). This radioisotopic assay for determination of DTH in vivo using 5-iodo-2'-deoxyuridine-'z51 ('"I...
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