Surfactant protein D deficiency influences allergic immune responses.
BACKGROUND
The collectin surfactant protein D (SP-D) confers protection against pulmonary infection and inflammation. Recent data suggest a role for SP-D in the modulation of allergic inflammation.


OBJECTIVE
The aim of this study is to characterize the immune responses of SP-D-deficient (SP-D(-/-)) mice in a kinetic model of allergic inflammation. We determined whether allergic parameters were enhanced in SP-D(-/-) mice in vivo. Further, we examined whether functional immune responses in vitro such as lymphocyte proliferation (LP) and cytokine production were modulated in the absence of SP-D.


METHODS
In vivo, wild-type (WT) and SP-D(-/-) mice were sensitized and challenged with the allergen ovalbumin (OVA) and assessed for allergic parameters (bronchoalveolar lavage (BAL) eosinophils, IL-13 production, pulmonary IFN-gamma, IL-10 expression) at early time points (1 and 3 days of challenge) in comparison with late time points (7 days of challenge). In vitro, spleen cells from WT and SP-D(-/-) mice were stimulated with the mitogen concanavalin A (ConA) and lipid A (LpA) and analysed for LP, IL-13 and IFN-gamma production. Toll-like receptor 4 (TLR4), ligand for LpA, was assessed by mRNA expression and immunohistochemistry in vivo.


RESULTS
Following allergen exposure in vivo, SP-D(-/-) mice expressed higher BAL eosinophils and IL-13 concentrations and lower IFN-gamma expression at early time points compared with WT mice. IL-10 expression was increased at early time points in SP-D(-/-) compared with WT mice. Allergen-induced TLR4 expression was increased in WT, but not in SP-D(-/-) mice. After stimulation with LpA and ConA in vitro LP was increased and IFN-gamma concentration was decreased in SP-D(-/-) mice.


CONCLUSIONS
SP-D may be critical for the modulation of early stages of allergic inflammation in vivo.
Schaub
B
B
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Westlake
R M
RM
He
H
H
Arestides
R
R
Haley
K J
KJ
Campo
M
M
Velasco
G
G
Bellou
A
A
Hawgood
S
S
Poulain
F R
FR
Perkins
D L
DL
Finn
P W
PW
D000818:Animals; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D049109:Cell Proliferation; D003208:Concanavalin A; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018793:Interleukin-13 / Q000276:immunology; D008050:Lipid A; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010047:Ovalbumin; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood / Q000235:genetics* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000032:analysis; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D018793:Interleukin-13; D008050:Lipid A; D008562:Membrane Glycoproteins; D037663:Pulmonary Surfactant-Associated Protein D; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D003208:Concanavalin A; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin