Coupling of the adhesive receptor CD11b/CD18 to functional enhancement of effector macrophage tissue factor response.
Initiation and regulation of localized selective proteolysis is an important effector property of cells of macrophage (Mo) lineage. Among such effector responses is the induced expression of tissue factor (TF) by cells of Mo lineage. In characterizing the regulation of the Mo responses that may influence the magnitude of the effector phase of the cellular immune response, we have identified a role for the cell surface adhesive receptor CD11b/CD18 (Mac-1, CR3) to amplify the induced TF response. Occupancy of CD11b/CD18 by MAb as surrogate ligands does not directly initiate a TF response. In contrast, after either T cell-derived cytokine or LPS as initial signals, engagement of CD11b/CD18 by MAb induces a two- to eight-fold functional enhancement of the TF response in murine and human Mo. This pathway of CD11b/CD18 enhancement of this Mo effector response was also confirmed with recognized ligands for CD11b/CD18 by exposure of Mo to immobilized fibrinogen. A quantitative increase of Mo surface expression of TF was validated by flow cytometry. We suggest that engagement of CD11b/CD18 by complementary ligands including adherence to extracellular matrix, and possibly in antigen-driven TH:Mo collaborative responses, results in the transduction of cellular signals that quantitatively enhance the expression of TF per se and thereby enhance the inflammatory component of Mo mediated response.
Fan
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Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Edgington
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D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D001779:Blood Coagulation Factors / Q000032:analysis / Q000096:biosynthesis*; D018821:CD18 Antigens; D002118:Calcium / Q000502:physiology; D005167:Factor VII / Q000096:biosynthesis; D005170:Factor X / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D013925:Thromboplastin / Q000096:biosynthesis*
D015703:Antigens, CD; D001779:Blood Coagulation Factors; D018821:CD18 Antigens; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D016028:Receptors, Leukocyte-Adhesion; C045072:macrophage procoagulant activity; D005167:Factor VII; D005170:Factor X; D013925:Thromboplastin; D002118:Calcium