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-γ 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.
|American Journal of Physiology - Lung Cellular and Molecular Physiology
|Published - 1995
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology