STUDIES ON THE PATHOGENESIS OF FEVER. 13. THE EFFECT OF PHAGOCYTOSIS ON THE RELEASE OF ENDOGENOUS PYROGEN BY POLYMORPHONUCLEAR LEUKOCYTES.
1. Phagocytosis promotes the release of endogenous pyrogen from polymorphonuclear leucocytes. 2. The release of pyrogen, though initiated by the phagocytic event, is not synchronous with it. 3. The postphagocytic release mechanism is not inhibited by sodium fluoride and, therefore, appears not to require continued production of energy by the cell. 4. The release process, on the other hand, is inhibited by arsenite, suggesting the participation of one or more sulfhydryl-dependent enzymes in the over-all reaction. 5. Particle for particle, the ingestion of heat-killed rough pneumococci causes the release of approximately 100 times as much pyrogen as the ingestion of polystyrene beads of the same size. 6. The pyrogen release mechanism of polymorphonuclear leucocytes separated directly from blood, unlike that of granulocytes in acute inflammatory exudates, is not readily activated by incubation of the cells in K-free saline. Despite this difference, both blood and exudate leucocytes following phagocytosis release large amounts of pyrogen, even in the presence of K(+). The fact that the postphagocytic reaction is uninhibited by the concentrations of K(+) which are present in plasma and extracellular fluids, suggests that this mechanism of pyrogen release may well operate in vivo. 7. As might be expected from the foregoing observations, the intravenous injection of a sufficiently large number of heat-killed pneumococci causes fever in the intact host. Intravenously injected polystyrene beads, on the other hand, are significantly less pyrogenic. Evidence is presented to support the conclusion that the fever in both instances is caused by pyrogen released from the circulating leucocytes which have phagocyted the injected particles. 8. The possible relationships of these findings to the pathogenesis of fevers caused by acute bacterial infections are discussed.
D000818:Animals; D001419:Bacteria; D001426:Bacterial Proteins; D002118:Calcium; D004492:Edetic Acid; D005122:Exudates and Transudates; D005334:Fever; D005459:Fluorides; D006651:Histocytochemistry; D007239:Infections; D007375:Interleukin-1; D007962:Leukocytes; D009504:Neutrophils; D010538:Peritonitis; D010587:Phagocytosis; D010949:Plasma; D010969:Plastics; D011188:Potassium; D011749:Pyrogens; D011817:Rabbits; D012106:Research; D012964:Sodium; D013296:Streptococcus pneumoniae; D013438:Sulfhydryl Compounds
D001426:Bacterial Proteins; D007375:Interleukin-1; D010969:Plastics; D011749:Pyrogens; D013438:Sulfhydryl Compounds; C008270:leukocyte endogenous mediator; D004492:Edetic Acid; D012964:Sodium; D005459:Fluorides; D011188:Potassium; D002118:Calcium
BACTERIA; BACTERIAL PROTEINS; CALCIUM; DIPLOCOCCUS PNEUMONIAE; EDTA; EXPERIMENTAL LAB STUDY; EXUDATES AND TRANSUDATES; FEVER; FLUORIDES; HISTOCYTOCHEMISTRY; INFECTION; LEUKOCYTES; PERITONITIS; PHAGOCYTOSIS; PLASMA; PLASTICS; POTASSIUM; PYROGENS; RABBITS; SODIUM; SULFHYDRYL COMPOUNDS