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Monoclonal antibody 5.5 reacts with p8,14, a myeloid molecule associated with some vascular endothelium
1Macrophage Laboratory, Imperial Cancer Research Fund, London, GB.
Abstract:
The movement of mononuclear phagocytes and neutrophils from the circulation into tissues is a process which is not completely understood. Monoclonal antibody 5.5 is specific for an 8/14-kDa molecule known variously as the CF antigen, L1 molecule or MRP8 and 14. We show that this molecule, which will be named p8,14 in this study, is expressed in all circulating monocytes and neutrophils as an intracellular product (as well as some types of epithelium). Tissue staining patterns suggest that when monocytes and neutrophils adhere to vascular endothelium, they release this molecule onto the associated endothelium. This process occurs with single monocytes and when monocytes form part of an inflammatory infiltrate. Monoclonal antibody 5.5 does not react with cultured endothelial cells even when stimulated with phorbol ester, tumor necrosis factor, interferon-gamma or interleukin 1 alpha providing further evidence that myeloid cells are the source of the p8,14 in this interactive process. Monocytes which have moved further into such tissues and tissue macrophages in general are monoclonal antibody 5.5 negative, suggesting that the ability to synthesize this molecule may be lost when monocytes leave the circulation and enter tissues. These results indicate that p8,14 plays a role in the interaction between myeloid cells and the vascular endothelium to which they adhere prior to leaving the circulation.
Insights
Myeloid cells release the p8,14 molecule onto vascular endothelium during inflammatory responses. This suggests p8,14 is crucial for myeloid cell adhesion and migration into tissues.
Area of Science:
- Immunology
- Cell Biology
Background:
- The transmigration of myeloid cells from circulation to tissues is not fully understood.
- Mononuclear phagocytes and neutrophils are key immune cells involved in inflammatory responses.
Purpose of the Study:
- To investigate the role of the 8/14-kDa molecule (p8,14) in myeloid cell interactions with vascular endothelium.
- To determine the source and expression patterns of p8,14 during inflammation.
Main Methods:
- Utilized monoclonal antibody 5.5, specific for the p8,14 molecule.
- Examined p8,14 expression in circulating myeloid cells and tissue-infiltrating cells.
- Analyzed p8,14 release onto vascular endothelium during cell adhesion.
Main Results:
- p8,14 is expressed intracellularly in circulating monocytes and neutrophils.
- Myeloid cells release p8,14 onto vascular endothelium upon adhesion.
- p8,14 expression is lost in tissue macrophages, suggesting downregulation post-migration.
Conclusions:
- p8,14 is released by myeloid cells and mediates their interaction with vascular endothelium.
- This interaction is critical for myeloid cell extravasation into tissues.
- p8,14 synthesis may be regulated by the transition from circulation to tissue.