Differential Regulation of the Mannose and SP-A Receptors on Macrophages

Am J Physiol. 1995 Dec;269(6 Pt 1):L721-6. doi: 10.1152/ajplung.1995.269.6.L721.


Two carbohydrate-dependent mechanisms exist on alveolar macrophages to clear mannose-containing pathogens: receptor-mediated entry of non-opsonized microorganisms via the mannose receptor and receptor recognition of pathogens opsonized with surfactant-associated protein A (SP-A). A number of studies have demonstrated that mannose receptor expression is tightly linked to the functional state of the macrophage. In the present study, we investigated regulation of binding of SP-A to its receptor on macrophages by the same agents that regulate mannose-receptor expression. Phorbol 12-myristate 13-acetate, lipopolysaccharide (LPS), and interferon-gamma treatment of rat marrow-derived macrophages increased SP-A binding by 163, 296, and 337%, respectively, over untreated controls. Mannose-receptor activity was reduced to 75, 60, and 25% of control levels by these agents. Dexamethasone increased mannose receptor activity to 225%, while decreasing SP-A binding to 44% of controls. Addition of granulocyte macrophage-colony stimulating factor (GM-CSF) to human monocytes on day 0 dramatically increased mannose-receptor activity on day 5 over the non-serum control. SP-A binding was highest to freshly isolated monocytes and decreased to < 10% after differentiation in the presence of GM-CSF. After intraperitoneal injection of dexamethasone, rat alveolar macrophages isolated at 24 h expressed increased mannose-receptor activity and decreased SP-A binding. LPS injection resulted in increased SP-A binding and decreased mannose-receptor activity. In every instance, SP-A binding was inversely regulated with respect to mannose-receptor expression. We therefore speculate that the mannose receptor is a first-line host-defense receptor that is turned off during inflammation. SP-A in the alveolar space can then act as a lung-specific opsonin and mediate clearance of pathogens via the upregulated SP-A receptor.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Horseradish Peroxidase / pharmacokinetics
  • Humans
  • Injections, Intraperitoneal
  • Interferon-gamma / pharmacology
  • Lectins, C-Type*
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / metabolism*
  • Macrophages, Alveolar / metabolism
  • Mannose-Binding Lectins*
  • Monocytes / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / metabolism*
  • Time Factors


  • Lectins, C-Type
  • Lipopolysaccharides
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • mannose receptor
  • surfactant protein A receptor
  • Dexamethasone
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Horseradish Peroxidase