title: Multiple receptors on human monocytes are involved in adhesion to cultured human endothelial cells.
abstract: Monocytes exhibit significant basal (unstimulated) adherence to human umbilical vein endothelium (HUVE), which is only partially inhibited by an anti-CD18 monoclonal antibody (mAb) (60.3). We examined factors modulating the residual, CD18-independent monocyte binding to HUVE by pretreating monocytes with mAb 60.3 to eliminate CD18-dependent binding. Basal adherence was reduced from 32% +/- 2% to 14% +/- 2% with mAb 60.3 (means +/- SE of eight experiments; P less than 0.01). mAb 60.3-treated monocytes were incubated with tumor necrosis factor-gamma (TNF-alpha), interleukin-1 (IL-1), lipopolysaccharide (LPS), N-formylmethionyl-leucyl-phenylalamine (FMLP), or phorbol myristate acetate (PMA). Only PMA affected CD18-independent binding. Pretreatment with PMA alone reduced adherence to 21% +/- 2% (mean +/- SE of eight experiments; P less than 0.01). In conjunction with mAb 60.3, PMA virtually eliminated monocyte adherence to HUVE (7% +/- 1%, mean +/- SE of eight experiments; P less than 0.01). We also examined CD18-independent monocyte binding to endothelial-leukocyte adhesion molecules (E-LAMs) induced by pretreatment of HUVE with LPS. Monoclonal antibody 60.3-treated monocytes increased adherence from 14% +/- 2% with unstimulated HUVE to 37% +/- 2% with LPS-stimulated HUVE (mean +/- SE of four experiments; P less than 0.01). Monocytes pretreated with both mAb 60.3 and PMA increased adherence from 5% +/- 1% with the unstimulated HUVE to 18% +/- 1% with the LPS-stimulated HUVE (mean +/- SE of four experiments; P less than 0.01). This result implies the presence of a CD18-independent and PMA-insensitive receptor on human monocytes for an E-LAM induced by LPS. In summary, we have identified two CD18-independent mechanisms of monocyte adherence to HUVE; a PMA-sensitive mechanism mediating basal adherence and a PMA-insensitive mechanism involved in binding to E-LAMs.
authors.affiliation: Department of Medicine, University of Washington, Seattle.
authors.forename: T M
authors.initials: TM
authors.lastname: Carlos
authors.forename: A
authors.initials: A
authors.lastname: Dobrina
authors.forename: R
authors.initials: R
authors.lastname: Ross
authors.forename: J M
authors.initials: JM
authors.lastname: Harlan
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000032:analysis; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000032:analysis / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014471:Umbilical Veins / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D018845:CD11 Antigens; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D013755:Tetradecanoylphorbol Acetate