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Further comparisons of endogenous pyrogens and leukocytic endogenous mediators
Abstract:
It was recently shown (Murphy et al., Infect. Immun. 34:177-183), that rabbit macrophages produce two biochemically and immunologically distinct endogenous pyrogens. One of these has or copurifies with substances having a molecular weight of 13,000 and a pI of 7.3. This protein was produced by blood monocytes or inflammatory cells elicited in 16-h rabbit peritoneal exudates. These acute peritoneal exudates were produced by the intraperitoneal injection of large volumes of saline containing shellfish glycogen. When the leukocytes in these exudates were washed and incubated at 37 degrees C in saline, they released an endogenous pyrogen. The injection of this pyrogen into rabbits, rats, or mice caused the biological manifestations which have been attributed to leukocytic endogenous mediator. These effects were increases in blood neutrophils, the lowering of plasma iron and zinc levels, and the increased synthesis of the acute-phase proteins. The other rabbit endogenous pyrogen seems to be a family of proteins with isoelectric points between 4.5 and 5.0. These proteins are produced by macrophages in the lung, liver, or in chronic peritoneal exudates. In these experiments, the lower-isoelectric-point endogenous pyrogens were produced by macrophages from the peritoneal cavity of rabbits that had been injected 4 days earlier with 50 ml of light mineral oil. These rabbit pyrogens were found to have leukocytic endogenous mediator activity in mice but to be completely inactive in rats. When injected into rabbits, these proteins produced fever, lowered plasma iron, increased blood neutrophils, but failed to elevate plasma fibrinogen.
Insights
Rabbit macrophages produce two distinct endogenous pyrogens. One pyrogen, from monocytes, mimics leukocytic endogenous mediator effects in multiple species, while the other, from lung/liver macrophages, shows species-specific activity.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages are key immune cells involved in inflammatory responses.
- Endogenous pyrogens are mediators of fever and acute-phase responses.
- Previous research indicated distinct pyrogen production by different cell types.
Purpose of the Study:
- To characterize the distinct endogenous pyrogens produced by rabbit macrophages.
- To investigate the biochemical and immunological properties of these pyrogens.
- To determine the biological activities and species-specific effects of the identified pyrogens.
Main Methods:
- Isolation and purification of endogenous pyrogens from rabbit macrophages.
- Biochemical characterization including molecular weight and isoelectric point determination.
- In vivo studies injecting pyrogens into rabbits, rats, and mice to assess biological effects.
Main Results:
- Two distinct endogenous pyrogens were identified: one with MW 13,000 and pI 7.3, and another as a family of proteins with pI 4.5-5.0.
- The high-pI pyrogen, produced by monocytes, induced fever, neutrophilia, and altered plasma zinc/iron levels in rabbits, rats, and mice.
- The low-pI pyrogens, from lung/liver macrophages, induced fever and neutrophilia in rabbits but were inactive in rats, and did not elevate plasma fibrinogen.
Conclusions:
- Rabbit macrophages produce at least two distinct endogenous pyrogens with differing biochemical properties and biological activities.
- The pyrogen produced by monocytes exhibits broad leukocytic endogenous mediator activity, while the macrophage-derived pyrogens show species-specific effects.
- These findings contribute to understanding the complex inflammatory mediator landscape and its differential regulation.