Myeloperoxidase mediates cell adhesion via the alpha M beta 2 integrin (Mac-1, CD11b/CD18).
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.
Johansson
M W
MW
Department of Physiological Botany, University of Uppsala, Villavägen 6, Sweden. mats.johansson@fysbot.uu.se
Patarroyo
M
M
Oberg
F
F
Siegbahn
A
A
Nilsson
K
K
D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D005434:Flow Cytometry; D018922:HL-60 Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D011956:Receptors, Cell Surface; D009195:Peroxidase