ABSTRACT
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. CONCLUSION: SP-D may be critical for the modulation of early stages of allergic inflammation in vivo.
Subject(s)
Asthma/immunology , Bronchoalveolar Lavage Fluid/immunology , Pulmonary Surfactant-Associated Protein D/genetics , Animals , Bronchial Provocation Tests , Cell Proliferation , Concanavalin A , Eosinophils/immunology , Female , Immunoglobulin E/blood , Interferon-gamma/analysis , Interleukin-10/analysis , Interleukin-13/immunology , Lipid A , Lymphocyte Activation , Male , Membrane Glycoproteins/analysis , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Ovalbumin , Pulmonary Surfactant-Associated Protein D/blood , Pulmonary Surfactant-Associated Protein D/immunology , Receptors, Cell Surface/analysis , Toll-Like Receptor 4 , Toll-Like ReceptorsABSTRACT
From January, 1987, until July, 1988, a significant increase in newly diagnosed cases of acute rheumatic fever was noted at our hospital. In sharp contrast to the 3 cases seen in 1986, 14 cases were diagnosed in 1987 (a significant increase from 1985 to 1986, P = 0.001). In the first 6 months of 1988 an additional 12 new cases were diagnosed (a further significant increase from 1987, P = 0.02). No further cases were diagnosed between July, 1988, and September, 1989. The major clinical manifestations were carditis in 73%, polyarthritis in 58% and chorea in 31%. In 15 of 26 patients an antecedent illness which included pharyngitis was noted; the remainder of patients were asymptomatic. Group A beta-hemolytic streptococci were isolated from 13 of 19 children cultured. Isolates from two patients with acute rheumatic fever were submitted for M typing: one isolate was mucoid M18/T18; the other isolate was a mucoid nontypable strain. The demographic characteristics of the 26 patients agree with classic descriptions in that patients were more likely to be urban, to come from large families and to have low incomes; racial breakdown of the group mirrored the Tennessee pediatric population. These characteristics stand in contrast to reports of recent outbreaks which describe suburban high income patients. These data suggest that practitioners should be again aware of acute rheumatic fever and that aggressive identification and treatment of streptococcal pharyngitis should continue to be a relevant public health concern.
