Related Experiment Videos
Adenosine and its derivatives control human monocyte differentiation into highly accessory cells versus macrophages
H M Najar1, S Ruhl, A C Bru-Capdeville
1Department of Immunology, University of Göttingen, West Germany.
Abstract:
Human peripheral blood monocytes have been found to undergo a transitory state of high accessory activity before they fully become macrophages. Time kinetics were done to follow this accessory potential. Studying the regulation of accessory activity, we have found that monocyte-derived accessory cells (m-AC) pass through two phases of development, which both are adversely controlled by cyclic nucleotides. Phase I is positively correlated by intracellular cAMP increase and can be arrested by adenosine 3';5' cyclic monophosphate (cAMP) and synergystic agents. In addition to cAMP, non-cyclic adenine nucleotides and adenosine also mimic all cAMP effects. This behavior is explained by the known presence of surface 5' nucleotidase and adenosine receptor, which in turn leads to activation of adenylate cyclase. At phase II serum is required to convert m-AC into macrophages. In the absence of serum, cells were arrested in the m-AC state. Adenine nucleotides effectively counteract the serum induction leading to the development of m-AC even in the presence of serum. Monocyte/macrophage markers such as Fc receptors and non-specific esterase strictly correlate negatively with the expression of accessory activity. Morphologically, the appearance of veils positively correlates with all experimental situations of high accessory activity. Therefore, it is evident that serum contains regulatory factors that strongly modify the accessory potency of the m-AC via the cyclic nucleotide system, thus presenting a potent immunoregulatory principle at the beginning of the immune cascade.
Insights
Human monocytes transition through accessory cell phases regulated by cyclic nucleotides. Serum influences this, but adenine nucleotides can maintain the accessory state, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human peripheral blood monocytes exhibit a transient phase of high accessory activity before differentiating into macrophages.
- This accessory potential is regulated by distinct developmental phases.
Purpose of the Study:
- To investigate the regulation of monocyte accessory activity during differentiation.
- To elucidate the role of cyclic nucleotides and serum in modulating monocyte-derived accessory cells (m-AC).
Main Methods:
- Kinetic studies to track accessory potential over time.
- Analysis of cyclic nucleotide effects (cAMP, adenine nucleotides, adenosine) on m-AC development.
- Investigation of serum's role in m-AC to macrophage conversion.
- Correlation of accessory activity with monocyte/macrophage markers (Fc receptors, non-specific esterase) and morphology (veils).
Main Results:
- Monocyte-derived accessory cells (m-AC) undergo two phases, both negatively controlled by cyclic nucleotides.
- Phase I accessory activity is enhanced by intracellular cAMP increase and can be inhibited by cAMP and related adenine nucleotides.
- Serum is required for Phase II conversion of m-AC to macrophages; adenine nucleotides counteract this serum induction, maintaining the m-AC state.
Conclusions:
- Serum contains regulatory factors that modulate m-AC accessory potency via the cyclic nucleotide system.
- This modulation represents a significant immunoregulatory principle at the initiation of the immune cascade.
- Accessory activity is inversely correlated with monocyte/macrophage markers and positively correlated with veil formation.