By DANIEL
نویسندگان
چکیده
Endogenous pyrogen (EP) 1 was first described by Beeson (1) in saline extracts of rabbit peritoneal exudate cells. These cells were >95% neutrophils, and it was assumed that neutrophils were the source of the pyrogen (1). A series of studies over the last 30 yr has established that EP is the common mediator of almost all febrile states that are not attributable to disorders of the thermoregulatory complex in the nervous system (2). We activated peritoneal exudate cells by using three different stimuli in the presence of radiolabeled amino acids. The EP were subsequently purified to homogeneity (3) and were shown to be radioactive. Furthermore, EP secreted in response to endotoxin, staphylococci, or tuberculin were identical. The purified EP had an 13,000 tool wt and an isoelectric point of 7.3 (4). We have recently shown that purified rabbit macrophages secreted four EP. One EP appeared to be identical with the EP previously purified from peritoneal exudate cells that were mostly neutrophils. The other EP were a family of proteins with isoelectric point (pI) values between 5.0 and 5.2. When macrophages were stimulated in the presence of radiolabeled amino acids, the purified pI 5.0-5.2 pyrogens aligned with peaks of radioactivity. This suggested that these EP were also synthesized de novo when the macrophages were stimulated. Also, EP from macrophages stimulated with endotoxin co-isoelectric focussed with EP from macrophages stimulated with staphylococci (5). Because macrophages appeared to make all the known EP, we reinvestigated the question of what EP neutrophils made, if any. We purified neutrophils and monocytes or macrophages from rabbit blood and from peritoneal exudates. We tested the purified neutrophils for pyrogen production and for various other functional activities. The results are described in this paper.
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