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Alpha-fetoprotein (AFP) in granulomatous inflammation of the mouse
J Trojan1, J Naval, H Jusforgues
1Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
Abstract:
Inflammatory granulomas constituted of various proportions of macrophages, polynuclear (PMNs) and mononuclear cells were induced in adult pathogen-free mice by injecting polyacrylamide beads into subcutaneous pouches. Using specific anti-mouse alpha-fetoprotein (AFP) antibodies, the presence of AFP was immunocytochemically demonstrated in the cytoplasm of macrophages and of immature PMNs (mature PMNs and mononuclear cells were AFP negative). AFP-labelling started as soon as 36 h after granuloma induction and reached a maximum 60-72 h later, to disappear on day 5. The examination of different organs in these mice also showed a transitory labelling for AFP of liver hepatocytes and of elements of kidney and of exocrine pancreas. Parallel to these findings, the selective concentration inside the granulomatous pouches of radiolabelled AFP injected in the course of inflammation was observed. These results suggest that (a) shortly after the inflammatory reaction the synthesis of AFP is resumed by the liver; (b) the newly synthesized AFP is secreted in the serum and preferentially taken up by the granulomas; and (c) consequently, in adult mice, AFP behaves as a positive acute phase reactant. The physiopathological implications of these facts are discussed in relation with the biological properties of AFP.
Insights
In adult mice, inflammation triggers liver alpha-fetoprotein (AFP) synthesis, which is then absorbed by granulomas, indicating AFP acts as an acute phase reactant.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- Inflammatory granulomas are complex cellular structures.
- Alpha-fetoprotein (AFP) is typically associated with fetal development.
- The role of AFP in adult inflammatory responses is not well understood.
Purpose of the Study:
- To investigate the presence and behavior of AFP during induced inflammation in adult mice.
- To determine if AFP synthesis or uptake changes in response to inflammatory stimuli.
- To explore the potential role of AFP as an acute phase reactant in adults.
Main Methods:
- Induction of inflammatory granulomas in adult mice using polyacrylamide beads.
- Immunocytochemical detection of AFP within granuloma cells using specific antibodies.
- Monitoring AFP expression kinetics post-granuloma induction.
- Organ examination for AFP labeling in liver, kidney, and pancreas.
- Tracking radiolabeled AFP uptake within granulomatous pouches.
Main Results:
- AFP was immunocytochemically detected in macrophages and immature polymorphonuclear neutrophils (PMNs) within granulomas.
- AFP labeling peaked between 36-72 hours after inflammation induction and diminished by day 5.
- Transitory AFP labeling was observed in liver hepatocytes, kidney, and pancreas elements.
- Radiolabeled AFP selectively concentrated within the induced granulomatous pouches.
Conclusions:
- Inflammatory stimuli in adult mice can induce a resurgence of liver AFP synthesis.
- Newly synthesized AFP is released into circulation and preferentially accumulates in inflammatory sites.
- These findings establish AFP as a positive acute phase reactant in adult mice during inflammation.