Heterodimers of the calcium-binding proteins MRP8 and MRP14 are expressed on the surface of human monocytes upon adherence to fibronectin and collagen. Relation to TNF-alpha, IL-6, and superoxide production.
The 27E10 antigen is a heterodimer of MRP8 and MRP14, two Ca(2+)-binding proteins related to the S-100 protein family. Previous studies have shown that 27E10 epitope-bearing monocyte subsets are prevalent in early acute but absent in chronic inflammatory conditions. These observations further provide an impetus for identifying the cellular mechanisms responsible for the appearance of different monocyte subpopulations during inflammation. Therefore this in vitro study was carried out to investigate the influence of adhesion in inducing 27E10-positive subsets. In adhesion assays the role of 27E10 antigen in spontaneous adherence was obvious, as a monoclonal antibody directed against the 27E10 antigen significantly inhibited the adherence of monocytes to collagen and fibronectin. In contrast, these extracellular matrix (ECM) proteins induce the cell surface expression and association of 27E10 antigen with cytoskeleton (CSK), detected by flow cytometry and confocal laser scan microscopy, respectively. Similar results were obtained on cross-linking with specific antibodies, thus showing involvement of the integrin molecules VLA-2 and VLA-4. In addition, the association with CSK could be confirmed by differential detergent extraction. The observed redistribution of 27E10 antigen guided by collagen compared with fibronectin was also paralleled by an augmented release of inflammatory cytokines interleukin-6, tumor necrosis factor alpha, and superoxide anions. Thus, this study demonstrates that under inflammatory conditions the interactions of extravasating monocytes with the ECM may induce an activated phenotype of monocytes marked by 27E10.
Mahnke
K
K
Institute of Experimental Dermatology, University of Muenster, Germany.
Bhardwaj
R
R
Sorg
C
C
D000941:Antigens / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D040501:Calgranulin A; D040502:Calgranulin B; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D018613:Microscopy, Confocal; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000941:Antigens; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D003094:Collagen