The Editors' choiceSurfactant protein D alters allergic lung responses in mice and human subjects
Section snippets
Patients
The inclusion criteria are as follows: (1) a diagnosis of asthma and (2) age greater than 5 years and less than 18 years. The exclusion criteria are as follows: (1) presence of a comorbid lung condition and (2) dependency on oral steroids or an immunosuppressive agent for a medical condition other than asthma. These children subsequently underwent skin prick testing to a panel of 11 relevant environmental antigens indigenous to the Ohio valley (Greer Laboratories, Lenoir, NC).
The patients in
Increased leukocytes in the lungs of naive SP-D–deficient mice
To uncover early events associated with the development of pulmonary inflammation, we focused our study on 4- to 5-week-old Sftpd−/− mice. A significant increase in cells recovered from the BALF of Sftpd−/− mice was already observed at 4 to 5 weeks of age (Fig 1, A). More than 97% of these BALF cells were macrophages. Although neutrophils were rare in naive wild-type mice (<1%), the percentage of BALF neutrophils was significantly higher in Sftpd−/− mice (Fig 1, B). Similarly, mucus-producing
Discussion
In the present study a human SP-D mutation (Met11Thr) that inhibits SP-D binding to pathogens14 was associated with decreased atopy and potentially asthma susceptibility. A recent German study concludes that none of the 3 known amino acid variants in SP-D are associated with bronchial asthma.27 However, the German control population was randomly selected and did not exclude all control subjects with a history of asthma.27 In the present study the control subjects were carefully selected but
References (40)
Role and regulation of lung collectins in allergic airway sensitization
Pharmacol Ther
(2006)- et al.
Spontaneous emphysema in surfactant protein D gene-targeted mice
Chest
(2000) - et al.
Surfactant protein-D regulates surfactant phospholipid homeostasis in vivo
J Biol Chem
(1998) - et al.
Endotoxin contamination of ovalbumin suppresses murine immunologic responses and development of airway hyper-reactivity
J Biol Chem
(2003) Mechanisms of the hygiene hypothesis—molecular and otherwise
Curr Opin Immunol
(2006)- et al.
The many faces of the hygiene hypothesis
J Allergy Clin Immunol
(2006) - et al.
The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung
J Clin Invest
(2002) - et al.
Surfactant proteins SP-A and SP-D in human health and disease
Arch Immunol Ther Exp (Warsz)
(2005) Immunoregulatory functions of surfactant proteins
Nat Rev Immunol
(2005)- et al.
Surfactant proteins SP-A and SP-D as modulators of the allergic inflammation in asthma
Pathobiology
(2002)
Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens
Clin Exp Immunol
Binding of rat and human surfactant proteins A and D to Aspergillus fumigatus conidia
Infect Immun
Surfactant protein D increases phagocytosis and aggregation of pollen-allergen starch granules
Am J Physiol Lung Cell Mol Physiol
Lung surfactant proteins A and D can inhibit specific IgE binding to the allergens of Aspergillus fumigatus and block allergen-induced histamine release from human basophils
Clin Exp Immunol
Surfactant protein D decreases pollen-induced IgE-dependent mast cell degranulation
Am J Physiol Lung Cell Mol Physiol
Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens
J Clin Invest
Therapeutic effect of surfactant protein D in allergic inflammation of mite-sensitized mice
Clin Exp Allergy
Surfactant protein D regulates airway function and allergic inflammation through modulation of macrophage function
Am J Respir Crit Care Med
A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D
J Immunol
Polymorphisms in the human surfactant protein-D (SFTPD) gene: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced
Immunogenetics
Cited by (47)
Surfactant proteins of the human larynx
2016, Annals of AnatomyCitation Excerpt :Furthermore, they suppress microbial growth indirectly by enhancing phagocytic uptake of pathogens by macrophages (Chroneos et al., 2010; Haagsman et al., 2008; Kuroki et al., 2007; Madsen et al., 2013; Wu et al., 2003). In addition, SP-A and D exhibit immune modulatory functions, either enhancing or reducing the immune response in order to maintain an inflammation free mucosal environment (Brandt et al., 2008; Lhert et al., 2007). The presence of surfactant proteins has meanwhile been demonstrated in a number of extrapulmonary tissues of the body, amongst them human nasal epithelium, digestive tract, mesentery, brain, lacrimal apparatus, gingiva and major salivary glands (Bourbon and Chailley-Heu, 2001; Bräuer et al., 2007a,b, 2012; Fisher and Mason, 1995; Schicht et al., 2013; Schob et al., 2013).
Key mediators in the immunopathogenesis of allergic asthma
2014, International ImmunopharmacologyCitation Excerpt :Conversely, another study showed that SP-D−/− mice had impaired Th2 responses and reduced inflammation after allergen challenge [81]. In human patients, SP-D inhibited the chemotaxis of eosinophils suggesting an anti-inflammatory role in the lungs of asthmatic subjects [82]. Children with decreased or absent SP-D in bronchoalveolar lavage fluid were found to have more frequent respiratory diseases [83].
Association of serum surfactant protein D and SFTPD gene variants with asthma in Danish children, adolescents, and young adults
2022, Immunity, Inflammation and DiseaseBronchial asthma and salivary surfactant protein d: Review article
2021, Egyptian Journal of Hospital MedicineAssociation between SP-A rs1965708 gene polymorphism and allergic rhinitis risk in Chinese population
2021, Journal of Clinical Laboratory Analysis
Supported in part by a grant from the Mechanism of Asthma and Allergic Inflammation (MAAI) 2005 Interest Section Award (E.B.B.), MECEH-Institutional NIEHS T32 ES10957-03 and CCHMC-Institutional NICHD T32 HD43005-01 grants (M.D.S.), as well as National Institutes of Health grants HL-63329 (J.A.W.), R01 AI42242, HL-076383, and AI057803 (M.E.R.).
Disclosure of potential conflict of interest: N. Wang has received research support from the National Institutes of Health. J. A. Whitsett has a US patent (no. 6,838,429; surfactant protein D and emphysema), has received research support from the National Institutes of Health; and is on the speakers' bureau for Abbott Laboratories. M. E. Rothenberg has consulting arrangements with Ception Therapeutics, GlaxoSmith-Kline, and MedaCorp; owns stock in Ception Therapeutics; is on the speakers' bureau for Merck; and has received honoraria from GlaxoSmithKline, Ception Therapeutics, and Merck. The rest of the authors have declared that they have no conflict of interest.