title: Haemoglobin triggers chemotaxis of human monocyte-derived dendritic cells: possible role in atherosclerotic lesion instability.
abstract: OBJECTIVE
  Mechanisms that drive innate immune cell recruitment into atherosclerotic lesions are still not well defined. We tested the role of haemoglobin (Hb) to promote chemotaxis, adhesion to endothelial cells and transendothelial migration of human monocytes and monocyte-derived immature dendritic cells (iDCs) and its possible role in atherogenic cell recruitment.
  
  
  RESULTS
  We demonstrated that Hb triggers chemotaxis, adhesion to endothelial cells and transendothelial migration of monocytes and monocyte-derived iDCs. Innate immune cell chemotaxis significantly increased in the presence of Hb in a dose-dependent manner involving extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) activation and actin remodeling. The pre-treatment of cells with pre-titrated concentration of the anti-CD163 blocking antibody reduced the Hb-induced cell migration, thus suggesting the involvement of CD163 receptor. Conversely, N-acetyl cysteine and soluble Hb-scavenger protein haptoglobin (Hp) inhibited the Hb-induced iDC migration. Finally, spontaneous iDC migration significantly increased in the presence of serum of patients with haemorrhagic complicated plaques and partially decreased in the presence of Hp.
  
  
  CONCLUSIONS
  Hb by interacting with CD163 on monocytes and iDCs might induce cell recruitment and activation within vascular wall, thus contributing to the complex cross talk of chemotactic signals that mediate atherosclerotic lesions instability.
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 299 Viale Regina Elena, Rome, Italy.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Buttari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Profumo
authors.forename: Claudio
authors.initials: C
authors.lastname: Di Cristofano
authors.forename: Donatella
authors.initials: D
authors.lastname: Pietraforte
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lionetti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capoano
authors.forename: Bruno
authors.initials: B
authors.lastname: Salvati
authors.forename: Rita
authors.initials: R
authors.lastname: Businaro
authors.forename: Gabriele
authors.initials: G
authors.lastname: Di Giammarco
authors.forename: Rachele
authors.initials: R
authors.lastname: Riganò
mesh_terms: D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003713:Dendritic Cells / Q000276:immunology*; D042783:Endothelial Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000166:cytology; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000276:immunology; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology; D000098902:CD163 Antigen
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006454:Hemoglobins; D011956:Receptors, Cell Surface; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases