Transendothelial migration of 27E10+ human monocytes.
The myeloid-related proteins MRP8 (S100A8) and MRP14 (S100A9), two members of the S100 family of calcium-binding proteins, are co-expressed and form a cell-surface and cytoskeleton-associated heterodimer upon calcium mobilization which is recognized by the mAb 27E10. The heterodimer is abundantly expressed in the cytoplasm of granulocytes and a subpopulation of blood monocytes. Previously, we and others demonstrated endothelium-associated MRP8/14 in inflamed tissues in the vicinity of transmigrating leukocytes, suggesting a function of the proteins in this process. Here, we demonstrate that 27E10(+) cells represent a fast-migrating monocyte subpopulation which preferentially utilizes an ICAM-1-dependent mechanism. The following observations imply a function of MRP8/14 in the transmigration process: (i) higher secretion of MRP8/14 from 27E10(+) monocytes compared to 27E10(-) monocytes after interaction with activated endothelium, (ii) higher expression of CD11b on 27E10(+) compared to 27E10(-) monocytes, (iii) up-regulation of CD11b on 27E10(-) monocytes in the presence of MRP14 or MRP8/14 heterodimers but not MRP8 and (iv) active participation of MRP14 but not of MRP8 in transmigration as shown by blocking with respective antibodies. We show that the interaction of 27E10(+) monocytes with activated endothelium leads to MRP8/14 release which may account for the high MRP8/14 concentrations in body fluids of patients with acute or chronic inflammatory diseases. Released MRP8/14 may serve a function by enhancing CD11b expression and/or affinity in human monocytes and by participating in the transendothelial migration mechanism. Thus, MRP8/14 substantially contributes to the recruitment of monocytes to an inflammatory site.
Eue
I
I
Institute of Experimental Dermatology, University of Münster, von-Esmarch-Strasse 56, 48149 Münster, Germany.
Pietz
B
B
Storck
J
J
Klempt
M
M
Sorg
C
C
D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins / Q000378:metabolism; D040501:Calgranulin A; D040502:Calgranulin B; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D019281:Dimerization; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D009000:Monocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D009418:S100 Proteins; D018799:Intercellular Adhesion Molecule-1