title: Pulmonary haptoglobin and CD163 are functional immunoregulatory elements in the human lung.
abstract: BACKGROUND
  The acute-phase protein haptoglobin (Hp) and its receptor CD163 serve as immunomodulators and possess anti-inflammatory besides antioxidant functions.
  
  
  OBJECTIVE
  To further understand the role of the recently described pulmonary Hp (pHp) and its receptor CD163 in case of inflammation and infection, pHp and CD163 were investigated on mRNA and protein level to gain insight into the cellular events taking place upon stimulation with the inflammatory mediators LPS, Pam3, cytokine IL-6 and dexamethasone, and upon infection with respiratory pathogens (Haemophilus influenzae, Streptococcuspneumoniae and Chlamydia pneumoniae) by use of a human ex vivo tissue culture model and cell cultures of A549 and alveolar epithelial cells type II. In addition, pHp and CD163 expression in COPD and sarcoidosis was assessed.
  
  
  METHODS
  We conducted experiments using 942 ex vivo cultured lung samples applying immunohistochemistry, immunocytochemistry, in situ hybridization, immunofluorescence, real-time PCR, RT-PCR, slot and Western immunoblot analyses with tissue lysates and culture supernatants as well as ELISA and cytometric bead array analyses.
  
  
  RESULTS
  This study describes for the first time the expression, regulation and secretion of pHp and its receptor CD163 in the human lung. The release of soluble mediators from A549 cell line and human monocyte-derived macrophages was observed indicating that Hp differentially activates the release of soluble mediators and major chemoattractants.
  
  
  CONCLUSIONS
  The findings indicate a native function of pHp and CD163 as functional pulmonary defense elements due to local expression, regulation and secretion during lung infection and as part of the inflammatory immune response of the respiratory system.
authors.affiliation: Clinical and Experimental Pathology, Research Center Borstel, Borstel, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Abdullah
authors.forename: D
authors.initials: D
authors.lastname: Kähler
authors.forename: C
authors.initials: C
authors.lastname: Vock
authors.forename: N
authors.initials: N
authors.lastname: Reiling
authors.forename: C
authors.initials: C
authors.lastname: Kugler
authors.forename: D
authors.initials: D
authors.lastname: Drömann
authors.forename: J
authors.initials: J
authors.lastname: Rupp
authors.forename: H P
authors.initials: HP
authors.lastname: Hauber
authors.forename: H
authors.initials: H
authors.lastname: Fehrenbach
authors.forename: P
authors.initials: P
authors.lastname: Zabel
authors.forename: E
authors.initials: E
authors.lastname: Vollmer
authors.forename: K
authors.initials: K
authors.lastname: Dalhoff
authors.forename: T
authors.initials: T
authors.lastname: Goldmann
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006242:Haptoglobins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D012141:Respiratory Tract Infections / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; D006242:Haptoglobins; D018836:Inflammation Mediators; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D012313:RNA