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Myeloperoxidase mediates cell adhesion via the alpha M beta 2 integrin (Mac-1, CD11b/CD18)
M W Johansson1, M Patarroyo, F Oberg
1Department of Physiological Botany, University of Uppsala, Villavägen 6, Sweden. mats.johansson@fysbot.uu.se
Abstract:
Myeloperoxidase is a leukocyte component able to generate potent microbicidal substances. A homologous invertebrate blood cell protein, peroxinectin, is not only a peroxidase but also a cell adhesion ligand. We demonstrate in this study that human myeloperoxidase also mediates cell adhesion. Both the human myeloid cell line HL-60, when differentiated by treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or retinoic acid, and human blood leukocytes, adhered to myeloperoxidase; however, undifferentiated HL-60 cells showed only minimal adhesion. No cells adhered to horseradish peroxidase, and cell adhesion to myeloperoxidase was not decreased by catalase, thus showing that peroxidase activity, per se, was neither sufficient nor necessary for the adhesion activity. Mannan, which has been reported to inhibit the binding of peroxidases to cells, did not affect adhesion to myeloperoxidase. However, adhesion to myeloperoxidase was inhibited by monoclonal antibodies to alpha M (CD11b) or to beta2 (CD18) integrin subunits, but not by antibodies to alpha L (CD11a), alpha M (CD11c), or to other integrins. Native myeloperoxidase mediated dose-dependent cell adhesion down to relatively low concentrations, and denaturation abolished the adhesion activity. It is evident that myeloperoxidase supports cell adhesion, a function which may be of considerable importance for leukocyte migration and infiltration in inflammatory reactions, that alpha M beta2 integrin (Mac-1 or CD11b/CD18) mediates this adhesion, and that the alphaM beta2 integrin-mediated adhesion to myeloperoxidase is distinct from the previously reported ability of this integrin to bind to certain denatured proteins at high concentrations.
Insights
Human myeloperoxidase (MPO) mediates leukocyte cell adhesion, a function crucial for inflammatory responses. This adhesion is specifically mediated by the alpha M beta 2 integrin (Mac-1), distinct from MPO
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Myeloperoxidase (MPO) is a key component of leukocytes, known for generating microbicidal substances.
- A related invertebrate protein, peroxinectin, functions as both a peroxidase and a cell adhesion molecule.
- The cell adhesion properties of human MPO have not been previously established.
Purpose of the Study:
- To investigate whether human myeloperoxidase (MPO) possesses cell adhesion properties.
- To identify the specific molecular mechanisms and cellular receptors involved in MPO-mediated cell adhesion.
Main Methods:
- Assessed adhesion of differentiated and undifferentiated HL-60 myeloid cells and human blood leukocytes to MPO.
- Utilized horseradish peroxidase as a control, and employed catalase to assess the role of peroxidase activity.
- Tested the effect of mannan and monoclonal antibodies targeting specific integrin subunits (alpha M [CD11b], beta 2 [CD18], alpha L [CD11a], alpha M [CD11c]).
- Evaluated the impact of MPO denaturation on cell adhesion.
Main Results:
- Differentiated HL-60 cells and human blood leukocytes adhered to MPO, while undifferentiated cells showed minimal adhesion.
- Peroxidase activity was neither sufficient nor necessary for MPO-mediated adhesion, as shown by controls with horseradish peroxidase and catalase.
- Mannan did not inhibit adhesion to MPO.
- Monoclonal antibodies against alpha M (CD11b) or beta 2 (CD18) integrin subunits, but not others, inhibited cell adhesion to MPO.
- Native MPO mediated dose-dependent adhesion, which was abolished upon denaturation.
- The alpha M beta 2 integrin (Mac-1) mediates this adhesion to MPO.
Conclusions:
- Human myeloperoxidase (MPO) functions as a cell adhesion molecule, independent of its enzymatic activity.
- Leukocyte adhesion to MPO is primarily mediated by the alpha M beta 2 integrin (Mac-1/CD11b/CD18).
- This MPO-mediated adhesion function is important for leukocyte migration and infiltration during inflammatory processes and represents a distinct interaction from previously known integrin-ligand binding.