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Using the radioactively-labeled alkaline-degraded acid-soluble fraction of amyloid ([ 125I ]DAA), we developed a radioimmunoassay for the previously described amyloid-related component of the human serum (SAA). Screening the sera of 228 normal individuals and of 297 patients with a variety of illnesses, we found that SAA is a component of all human sera, including cord blood (mean 94 plus or minus 57 ng/ml). The concentration of this component increases significantly with the aging process, reaching very high levels in the eighth and nine decades. It is also elevated in all cases of amyloidosis (except for those associated with nephrotic syndrome) as well as in many patients with myeloma, macroglobulinemia, lymphoma, carcinoma, rheumatoid arthritis, and tuberculosis. A marked increase was noted in the early stages of a variety of acute inflammatory and infectious states with a return to normal levels paralleling clinical improvement and faster than the erythrocyte sedimentation rate. The possible implications of this component in the genesis of amyloid and in the immune process are discussed.

In this study the presence of an amyloid A, antigenically related material was determined in four subpopulations of human leukocytes. Monocytes, granulocytes, thymus-derived lymphocytes, and bone marrow-derived and null lymphocytes were isolated from the peripheral blood of five apparently normal subjects, two patients with secondary amyloidosis, three patients with acute infections, and seven patients with metastatic cancer. Mononuclear leukocytes, isolated from the interface of a Ficoll-Hypaque gradient, were separated into monocytes, thymus-derived lymphocytes, and bone marrow-derived plus null lymphocytes by glass adherence and depletion of sheep erythrocyte rosette-forming lymphocytes. Granulocytes were isolated by sedimentation in 2% methyl cellulose from the erythrocyte-rich pellet formed at the bottom of the Ficoll-Hypaque gradient. The four isolated leukocyte subpopulations were cultured and, at varying intervals, the amyloid A content of the culture medium and of sonicated, 2 x 10(6) cells was determined by radioimmunoassay. Our results indicated a 2-14 times greater amount of amyloid A-related material in the sonicated granulocytes compared with the individuals' serum amyloid A levels. The mononuclear subpopulations showed a low or negligible amyloid A content. The amount of amyloid A antigenic material was further found to increase in cultured granulocytes, reaching a peak value between the 16th and 30th h of culture. The granulocytes of only two out of eight individuals tested released amyloid A antigenically related material into the culture medium. This release was found to be blocked by the presence of colchicine, vincristine, puromycin, or cycloheximide in the culture medium. In contrast, only the presence of puromycin or cycloheximide was shown to significantly inhibit the intracellular increase of amyloid A in the cultured granulocytes. Thus, it appears that among the circulating blood cells, the granulocytes produce amyloid A antigenically related material and could release it under conditions that remain to be further defined.