title: SP-D and regulation of the pulmonary innate immune system in allergic airway changes.
abstract: The airway mucosal surfaces are constantly exposed to inhaled particles that can be potentially toxic, infectious or allergenic and should elicit inflammatory changes. The proximal and distal air spaces, however, are normally infection and inflammation free due to a specialized interplay between cellular and molecular components of the pulmonary innate immune system. Surfactant protein D (SP-D) is an epithelial-cell-derived immune modulator that belongs to the small family of structurally related Ca(2+)-dependent C-type collagen-like lectins. While collectins can be detected in mucosal surfaces of various organs, SP-A and SP-D (the 'lung collectins') are constitutively expressed in the lung at high concentrations. Both proteins are considered important players of the pulmonary immune responses. Under normal conditions however, SP-A-/- mice display no pathological features in the lung. SP-D-/- mice, on the other hand, show chronic inflammatory alterations indicating a special importance of this molecule in regulating immune homeostasis and the function of the innate immune cells. Recent studies in our laboratory and others implied significant associations between changes in SP-D levels and the presence of airway inflammation both in animal models and patients raising a potential usefulness of this molecule as a disease biomarker. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-D binds carbohydrates, lipids and nucleic acids with a broad spectrum specificity and initiates phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional over expressor mice in addition, provided evidence that SP-D directly modulates macrophage and dendritic cell function as well as T cell-dependent inflammatory events. Thus, SP-D has a unique, dual functional capacity to induce pathogen elimination on the one hand and control of pro-inflammatory mechanisms on the other, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation without compromising the host defence function of the airways. This paper will review recent findings on the mechanisms of immune-protective function of SP-D in the lung.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Forbes
authors.forename: A
authors.initials: A
authors.lastname: Haczku
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology*
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D
references.citation: Am J Physiol. 1999 Jan;276(1):L164-74
references.pmid: 9887069
references.citation: Pediatr Res. 2002 Jun;51(6):696-9
references.pmid: 12032263
references.citation: J Biol Chem. 1987 Feb 25;262(6):2582-9
references.pmid: 3029088
references.citation: Biochem Biophys Res Commun. 1987 Apr 14;144(1):367-74
references.pmid: 3579914
references.citation: Environ Health Perspect. 2008 Jun;116(6):799-805
references.pmid: 18560537
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Oct;283(4):L755-65
references.pmid: 12225952
references.citation: Biochem Soc Trans. 2002 Nov;30(Pt 6):1010-4
references.pmid: 12440963
references.citation: J Immunol. 2001 Nov 15;167(10):5868-73
references.pmid: 11698462
references.citation: J Immunol. 2002 Sep 15;169(6):3267-74
references.pmid: 12218146
references.citation: Pharmacol Ther. 2006 Apr;110(1):14-34
references.pmid: 16226313
references.citation: Nat Rev Immunol. 2005 Jan;5(1):58-68
references.pmid: 15630429
references.citation: J Biol Chem. 1986 Jul 5;261(19):9029-33
references.pmid: 3755136
references.citation: Clin Exp Allergy. 2004 Dec;34(12):1819-26
references.pmid: 15663554
references.citation: Am J Respir Cell Mol Biol. 1999 Sep;21(3):380-7
references.pmid: 10460755
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Sep;281(3):L697-703
references.pmid: 11504698
references.citation: J Allergy Clin Immunol. 2004 Mar;113(3):439-44
references.pmid: 15007344
references.citation: Thorax. 1990 Jan;45(1):3-8
references.pmid: 2321174
references.citation: Nat Rev Mol Cell Biol. 2001 Aug;2(8):627-33
references.pmid: 11483996
references.citation: J Immunol. 2005 Jun 1;174(11):6943-54
references.pmid: 15905537
references.citation: Chest. 2002 Mar;121(3 Suppl):89S
references.pmid: 11893715
references.citation: Infect Immun. 2004 Jan;72(1):145-53
references.pmid: 14688091
references.citation: J Immunol. 2002 Oct 1;169(7):3978-86
references.pmid: 12244199
references.citation: Immunobiology. 2002 Sep;205(4-5):610-8
references.pmid: 12396019
references.citation: Biochemistry. 1988 Nov 15;27(23):8576-84
references.pmid: 3219363
references.citation: Am J Respir Cell Mol Biol. 1998 Oct;19(4):700-8
references.pmid: 9761768
references.citation: Am J Respir Cell Mol Biol. 2001 Jul;25(1):45-50
references.pmid: 11472974
references.citation: Am J Physiol. 1994 Feb;266(2 Pt 1):L148-55
references.pmid: 8141310
references.citation: Am J Physiol. 1994 Dec;267(6 Pt 1):L712-9
references.pmid: 7810675
references.citation: Ann N Y Acad Sci. 2003 Dec;1010:471-5
references.pmid: 15033772
references.citation: J Immunol. 1995 Dec 1;155(11):5343-51
references.pmid: 7594549
references.citation: PLoS Biol. 2008 Nov 11;6(11):e266
references.pmid: 19007302
references.citation: Mol Immunol. 2006 Mar;43(9):1293-315
references.pmid: 16213021
references.citation: Eur J Biochem. 2004 Apr;271(7):1229-49
references.pmid: 15030473
references.citation: J Mol Evol. 1998 Feb;46(2):131-8
references.pmid: 9452514
references.citation: Eur J Immunol. 1992 Jun;22(6):1437-45
references.pmid: 1601034
references.citation: Am J Physiol. 1998 Jun;274(6):L958-69
references.pmid: 9609735
references.citation: Curr Drug Targets. 2008 Feb;9(2):113-22
references.pmid: 18288962
references.citation: Cell Microbiol. 2007 Aug;9(8):1871-9
references.pmid: 17490408
references.citation: Infect Immun. 2004 Feb;72(2):645-50
references.pmid: 14742504
references.citation: J Allergy Clin Immunol. 2008 Sep;122(3):521-528
references.pmid: 18554706
references.citation: Eur J Cell Biol. 2007 Dec;86(11-12):719-30
references.pmid: 17689829
references.citation: J Biol Chem. 2001 Jun 8;276(23):19862-70
references.pmid: 11279100
references.citation: J Infect Dis. 2000 Nov;182(5):1473-8
references.pmid: 11023470
references.citation: Microbes Infect. 2001 Feb;3(2):161-6
references.pmid: 11251302
references.citation: J Biol Chem. 2007 Dec 21;282(51):36808-19
references.pmid: 17848554
references.citation: J Immunol. 2009 Feb 15;182(4):2277-87
references.pmid: 19201882
references.citation: Nat Rev Immunol. 2008 May;8(5):362-71
references.pmid: 18379575
references.citation: Am J Physiol. 1997 May;272(5 Pt 1):L996-1004
references.pmid: 9176266
references.citation: Respir Res. 2003 Dec 08;4:15
references.pmid: 14748931
references.citation: Biochem J. 2001 Oct 1;359(Pt 1):243-8
references.pmid: 11563989
references.citation: Proc Natl Acad Sci U S A. 1985 Oct;82(19):6379-83
references.pmid: 3863100
references.citation: Biol Neonate. 2000 May;77 Suppl 1:9-13
references.pmid: 10828580
references.citation: Am J Respir Cell Mol Biol. 2007 Jan;36(1):94-102
references.pmid: 16902193
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Nov;285(5):L1066-76
references.pmid: 12871854
references.citation: Infect Immun. 2001 Jan;69(1):24-33
references.pmid: 11119485
references.citation: Am J Physiol. 1993 Apr;264(4 Pt 1):L338-44
references.pmid: 8476070
references.citation: Thorax. 1988 May;43(5):354-9
references.pmid: 3194863
references.citation: J Biol Chem. 2004 Jul 30;279(31):32728-36
references.pmid: 15145932
references.citation: J Biol Chem. 1996 Mar 22;271(12):6679-85
references.pmid: 8636086
references.citation: FASEB J. 2009 May;23(5):1415-30
references.pmid: 19126597
references.citation: Annu Rev Immunol. 2003;21:547-78
references.pmid: 12524383
references.citation: Proc Natl Acad Sci U S A. 1961 Nov 15;47:1858-9
references.pmid: 14456669
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11869-74
references.pmid: 9751757
references.citation: J Immunol. 2002 Jun 15;168(12):5989-92
references.pmid: 12055204
references.citation: J Biol Chem. 1997 May 23;272(21):13743-9
references.pmid: 9153228
references.citation: Infect Immun. 1995 Sep;63(9):3360-6
references.pmid: 7642263
references.citation: Biochem Biophys Res Commun. 1978 Apr 14;81(3):1018-24
references.pmid: 666781
references.citation: Am J Respir Cell Mol Biol. 1999 Feb;20(2):279-86
references.pmid: 9922219
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12889-94
references.pmid: 14561893
references.citation: Dis Markers. 1999 Dec;15(4):269-81
references.pmid: 10689550
references.citation: Am J Physiol. 1994 Dec;267(6 Pt 1):L660-6
references.pmid: 7810671
references.citation: J Allergy Clin Immunol. 2008 Nov;122(5):861-79; quiz 880-1
references.pmid: 19000577
references.citation: J Immunol. 2002 Sep 15;169(6):2892-9
references.pmid: 12218102
references.citation: Am J Respir Cell Mol Biol. 1999 May;20(5):953-63
references.pmid: 10226065
references.citation: J Biol Chem. 2002 Jun 21;277(25):22453-9
references.pmid: 11956209
references.citation: Am J Respir Crit Care Med. 2003 Oct 1;168(7):783-9
references.pmid: 12882759
references.citation: Infect Immun. 2001 Apr;69(4):2037-44
references.pmid: 11254556
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1453-63
references.pmid: 11704542
references.citation: Ann N Y Acad Sci. 2003 Dec;1010:113-6
references.pmid: 15033705
references.citation: Am J Respir Cell Mol Biol. 1999 Jan;20(1):90-8
references.pmid: 9870921
references.citation: Immunopharmacology. 1997 Dec;38(1-2):73-80
references.pmid: 9476117
references.citation: J Allergy Clin Immunol. 2008 May;121(5):1140-1147.e2
references.pmid: 18355911
references.citation: Clin Exp Immunol. 1988 Dec;74(3):465-70
references.pmid: 3069255
references.citation: Am J Respir Cell Mol Biol. 1999 Nov;21(5):576-85
references.pmid: 10536117
references.citation: J Clin Invest. 2001 Feb;107(4):467-75
references.pmid: 11181646
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Apr;288(4):L692-8
references.pmid: 15591410
references.citation: J Immunol. 1999 Oct 15;163(8):4495-502
references.pmid: 10510392
references.citation: Glycobiology. 1999 Dec;9(12):1357-69
references.pmid: 10561461
references.citation: Curr Opin Immunol. 2001 Feb;13(1):114-9
references.pmid: 11154927
references.citation: Am J Respir Cell Mol Biol. 1990 Jan;2(1):91-8
references.pmid: 2306370
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Aug;279(2):L216-23
references.pmid: 10926544
references.citation: Am J Respir Crit Care Med. 2008 Jul 15;178(2):158-67
references.pmid: 18420961
references.citation: J Biol Chem. 2000 Jul 21;275(29):22442-51
references.pmid: 10801802
references.citation: Biochem Biophys Res Commun. 1994 Aug 15;202(3):1674-80
references.pmid: 8060356
references.citation: J Immunol. 2006 Mar 15;176(6):3557-65
references.pmid: 16517724
references.citation: Clin Exp Immunol. 2003 Nov;134(2):181-7
references.pmid: 14616775
references.citation: Cell. 2002 Dec 27;111(7):927-30
references.pmid: 12507420
references.citation: Am J Respir Cell Mol Biol. 2001 Apr;24(4):475-84
references.pmid: 11306442
references.citation: J Immunol. 1998 Nov 1;161(9):4599-603
references.pmid: 9794387
references.citation: Arch Biochem Biophys. 1991 Oct;290(1):116-26
references.pmid: 1898081
references.citation: Eur J Immunol. 2003 Oct;33(10):2853-63
references.pmid: 14515269
references.citation: J Leukoc Biol. 2001 Jul;70(1):135-41
references.pmid: 11435496
references.citation: Cell. 2003 Oct 3;115(1):13-23
references.pmid: 14531999
references.citation: J Immunol. 2002 Oct 1;169(7):3565-73
references.pmid: 12244146
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Jun;280(6):L1148-56
references.pmid: 11350793
references.citation: Respir Res. 2008 Jan 28;9:13
references.pmid: 18226251
references.citation: J Immunol. 2007 Aug 1;179(3):1438-48
references.pmid: 17641009
references.citation: J Clin Invest. 2000 Aug;106(4):551-9
references.pmid: 10953030
references.citation: Biosci Rep. 1993 Apr;13(2):79-90
references.pmid: 8374060
references.citation: J Immunol. 1997 May 1;158(9):4336-40
references.pmid: 9126996
references.citation: Clin Exp Immunol. 2002 Oct;130(1):19-24
references.pmid: 12296848
references.citation: Am J Respir Cell Mol Biol. 1996 Jul;15(1):115-21
references.pmid: 8679215
references.citation: Infect Immun. 2001 Apr;69(4):2728-31
references.pmid: 11254642
references.citation: Infect Immun. 2001 Mar;69(3):1587-92
references.pmid: 11179331
references.citation: Clin Exp Immunol. 1996 Nov;106(2):367-73
references.pmid: 8918587
references.citation: Immunol Lett. 2003 May 1;86(3):299-307
references.pmid: 12706535
references.citation: Chest. 2000 May;117(5 Suppl 1):249S-50S
references.pmid: 10843936
references.citation: Bioessays. 2007 May;29(5):452-64
references.pmid: 17450595
references.citation: Biochem Soc Trans. 1997 Nov;25(4):S656
references.pmid: 9450084
references.citation: Biochem Biophys Res Commun. 2000 Apr 21;270(3):831-5
references.pmid: 10772911
references.citation: Eur Respir J. 2001 Sep;18(3):482-90
references.pmid: 11589345
references.citation: APMIS Suppl. 2000;100:1-59
references.pmid: 11021254
references.citation: Infect Immun. 2003 Apr;71(4):1662-71
references.pmid: 12654779
references.citation: Respir Res. 2006 Jun 01;7:85
references.pmid: 16740162
references.citation: Annu Rev Physiol. 2001;63:495-519
references.pmid: 11181965
references.citation: Am J Physiol. 1998 Oct;275(4):L679-86
references.pmid: 9755099
references.citation: Biochemistry. 2006 Jul 18;45(28):8657-64
references.pmid: 16834340
references.citation: Eur J Immunol. 2003 Aug;33(8):2327-36
references.pmid: 12884308
references.citation: Annu Rev Physiol. 2001;63:521-54
references.pmid: 11181966
references.citation: J Biol Chem. 1994 Jun 24;269(25):17311-9
references.pmid: 8006040
references.citation: J Clin Invest. 1992 Jul;90(1):97-106
references.pmid: 1634623
references.citation: J Biol Chem. 2002 Jul 26;277(30):26971-9
references.pmid: 12015304
references.citation: Immunity. 2007 Jun;26(6):741-50
references.pmid: 17582346
references.citation: J Immunol. 2000 Oct 1;165(7):3934-40
references.pmid: 11034401
references.citation: J Immunol. 2001 Feb 15;166(4):2727-33
references.pmid: 11160338
references.citation: Adv Immunol. 2007;93:265-78
references.pmid: 17383544
references.citation: J Allergy Clin Immunol. 2006 Aug;118(2):331-6
references.pmid: 16890754
references.citation: Infect Immun. 1997 Aug;65(8):3171-9
references.pmid: 9234771
references.citation: Nature. 1985 Sep 26-Oct 2;317(6035):361-3
references.pmid: 2995821
references.citation: Am J Physiol. 1997 May;272(5 Pt 1):L989-95
references.pmid: 9176265
references.citation: J Biol Chem. 2002 Mar 1;277(9):6830-7
references.pmid: 11724772
references.citation: Biochem J. 1994 Oct 15;303 ( Pt 2):407-11
references.pmid: 7980398
references.citation: J Exp Med. 2001 Sep 17;194(6):781-95
references.pmid: 11560994
references.citation: Respir Res. 2005 Aug 24;6:97
references.pmid: 16120217
references.citation: J Biol Chem. 1989 Aug 15;264(23):13923-8
references.pmid: 2788165
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Jan;284(1):L232-41
references.pmid: 12388334
references.citation: J Biol Chem. 2000 Dec 8;275(49):38848-55
references.pmid: 10969075
references.citation: Clin Exp Allergy. 2005 Apr;35(4):515-21
references.pmid: 15836762
references.citation: J Exp Med. 1990 Sep 1;172(3):955-9
references.pmid: 2388038
references.citation: Microbiol Mol Biol Rev. 1997 Sep;61(3):281-93
references.pmid: 9293182
references.citation: Am J Respir Cell Mol Biol. 1999 Apr;20(4):759-68
references.pmid: 10101009
references.citation: Biochemistry. 2001 Jul 3;40(26):7789-98
references.pmid: 11425305
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Nov;283(5):L1002-10
references.pmid: 12376353
references.citation: Am J Respir Crit Care Med. 1998 Aug;158(2):510-8
references.pmid: 9700129
references.citation: Am J Respir Cell Mol Biol. 2000 Dec;23(6):772-9
references.pmid: 11104730
references.citation: Am J Physiol. 1996 Aug;271(2 Pt 1):L310-9
references.pmid: 8770070
references.citation: J Biol Chem. 2002 Oct 11;277(41):38709-13
references.pmid: 12163500
references.citation: Pathobiology. 2002-2003;70(5):287-92
references.pmid: 12771511
references.citation: Pediatr Res. 2003 Mar;53(3):463-7
references.pmid: 12595595
references.citation: Protein Sci. 2000 Sep;9(9):1607-17
references.pmid: 11045608
references.citation: Am J Respir Cell Mol Biol. 1998 Aug;19(2):177-201
references.pmid: 9698590
references.citation: Am J Respir Cell Mol Biol. 2002 Jul;27(1):24-33
references.pmid: 12091242
references.citation: Mol Immunol. 2007 Jan;44(1-3):44-56
references.pmid: 16889830
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Nov;289(5):L856-66
references.pmid: 15980037
references.citation: J Immunol. 2002 Nov 15;169(10):5844-50
references.pmid: 12421966
references.citation: Am J Respir Cell Mol Biol. 2002 Mar;26(3):277-82
references.pmid: 11867335
references.citation: J Biol Chem. 2001 Jun 1;276(22):19214-9
references.pmid: 11278637
references.citation: J Infect Dis. 2004 Apr 15;189(8):1528-39
references.pmid: 15073692
references.citation: Arch Dis Child. 2003 Nov;88(11):981-4
references.pmid: 14612363
references.citation: J Biol Chem. 1995 Aug 11;270(32):19052-8
references.pmid: 7642568
references.citation: N Engl J Med. 1965 Jun 24;272:1336-7
references.pmid: 14299144
references.citation: J Immunol. 2005 Feb 1;174(3):1532-8
references.pmid: 15661913
references.citation: Infect Immun. 1999 Sep;67(9):4563-9
references.pmid: 10456901
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Feb;278(2):L365-73
references.pmid: 10666121
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Oct;285(4):L854-61
references.pmid: 12794007
references.citation: Biochem J. 1992 Aug 15;286 ( Pt 1):5-8
references.pmid: 1325783
references.citation: Am J Respir Cell Mol Biol. 1995 Apr;12(4):410-5
references.pmid: 7695920
references.citation: Respirology. 2006 Jan;11 Suppl:S37-40
references.pmid: 16423269
references.citation: Trends Cell Biol. 2009 Feb;19(2):72-80
references.pmid: 19144521