Eric B. Brandt, PhD, Melissa K. Mingler, MS, Michelle D

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Surfactant protein D alters allergic lung responses in mice and human subjects Eric B. Brandt, PhD, Melissa K. Mingler, MS, Michelle D. Stevenson, MD, Ning Wang, PhD, Gurjit K. Khurana Hershey, MD, PhD, Jeffrey A. Whitsett, MD, Marc E. Rothenberg, MD, PhD Journal of Allergy and Clinical Immunology Volume 121, Issue 5, Pages 1140-1147.e2 (May 2008) DOI: 10.1016/j.jaci.2008.02.011 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Pulmonary inflammation in naive Sftpd−/− mice. A, Total cell counts. B, Neutrophil BALF percentages. Percentage of positive CD4 (C) and CD4/CD69 (D) lung cells (n = 6-9; ∗∗P < .01, ∗∗∗P < .001). E, Representative density plots of CD69+ cells. F, Representative pictures of PAS-stained large upper airways of wild-type and Sftpd−/− mice (×40 magnification). WT, Wild-type; KO, knockout; PE, phycoerythrin; FITC, fluorescein isothiocyanate. Journal of Allergy and Clinical Immunology 2008 121, 1140-1147.e2DOI: (10.1016/j.jaci.2008.02.011) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Baseline chemokine and cytokine levels in lung homogenates of wild-type and Sftpd−/− mice. Lung levels of CCL2/JE/monocyte chemoattractant protein 1 (A), CCL17/TARC (B), IL-4 (C), IL-13 (D), IFN-γ (E), and IL-12p70 (F) in 4- to 5-week-old (open circles, n = 4) and 6- to 7-week-old (solid circles, n = 4) Sftpd−/− mice and wild-type control animals. WT, Wild-type; KO, knockout. Journal of Allergy and Clinical Immunology 2008 121, 1140-1147.e2DOI: (10.1016/j.jaci.2008.02.011) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Impaired systemic TH2 profile in naive Sftpd−/− mice. Total plasma IgE (A) and IgG1 (B) levels were measured in 4- to 5-week-old mice. Spleen cells were stimulated with anti-CD3 and anti-CD28, and IL-4 (C), IL-13 (D), and IFN-γ (E) levels were measured in culture supernatants (n = 12-26). ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. WT, Wild-type; KO, knockout. Journal of Allergy and Clinical Immunology 2008 121, 1140-1147.e2DOI: (10.1016/j.jaci.2008.02.011) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Decreased allergic airway responses in Sftpd−/− mice after repeated A fumigatus exposures. A, Protocol. Total BALF cells (B), eosinophils (C), and IL-13 (E) BALF levels in Sftpd−/− mice and their control animals. D, Number of eosinophils per square millimeter around small airways. F, Mucus production was expressed as a percentage of PAS-positive small airway epithelial cells. G, Airway resistance to a methacholine dose of 100 mg/mL (n = 7-18). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001. ns, Not significant. Journal of Allergy and Clinical Immunology 2008 121, 1140-1147.e2DOI: (10.1016/j.jaci.2008.02.011) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions