Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation.
Mast cells play a key role in allergy and asthma. They reside at the host-environment interface and are among the first cells to make contact with inhaled microorganisms and particulate antigens. Pulmonary surfactant proteins A and D (SP-A and SP-D) function in lung host defense by enhancing microbe phagocytosis and mediating other immune cell functions, but little is known about their effects on mast cells. We hypothesized that SP-A and/or SP-D modulate IgE-dependent mast cell functions. Pollen starch granules (PSG) extracted from Dactylis glomerata and coated with trinitrophenol (TNP) were used as a model of an inhaled organic particulate allergen. Our data revealed that SP-D inhibited by 50% the release of beta-hexosaminidase by peritoneal mast cells sensitized with IgE anti-TNP and stimulated with TNP-PSG. In contrast, SP-A had no effect. Furthermore, SP-D aggregated PSG in a dose-dependent manner, and this aggregation was mediated by SP-D's carbohydrate recognition domain. A single arm SP-D mutant (RrSP-Dser15,20) neither aggregated PSG nor inhibited degranulation, suggesting that multimerization of SP-D is required for maximal PSG aggregation and inhibition of PSG-induced mast cell degranulation. This study is the first to demonstrate that SP-D modulates IgE-mediated mast cell functions, which are important in asthma and allergic inflammation.
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Delphine C
DC
Malherbe
Veit J
VJ
Erpenbeck
Soman N
SN
Abraham
Erika C
EC
Crouch
Jens M
JM
Hohlfeld
Jo Rae
JR
Wright
D000818:Animals; D001665:Binding Sites; D015550:Cell Degranulation / Q000187:drug effects*; D002478:Cells, Cultured; D007073:Immunoglobulin E / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D011058:Pollen / Q000009:adverse effects / Q000276:immunology; D020836:Protein Structure, Quaternary; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology
D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins; D007073:Immunoglobulin E