This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lekkala, M.
Right arrow Articles by Stevens, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lekkala, M.
Right arrow Articles by Stevens, D. A.

 Previous Article  |  Next Article 

Infection and Immunity, August 2006, p. 4549-4556, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00243-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Effect of Lung Surfactant Collectins on Bronchoalveolar Macrophage Interaction with Blastomyces dermatitidis: Inhibition of Tumor Necrosis Factor Alpha Production by Surfactant Protein D

Madhavi Lekkala,1 Ann Marie LeVine,2 Michael J. Linke,3 Erika C. Crouch,4 Bruce Linders,4 Elmer Brummer,1,5 and David A. Stevens1,5*

Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, and California Institute for Medical Research, San Jose, California,1 Division of Pulmonary Biology and Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio,2 Veterans Affairs Medical Center, Cincinnati, Ohio,3 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri,4 Department of Medicine, Stanford University School of Medicine, Stanford, California5

Received 14 February 2006/ Returned for modification 18 March 2006/ Accepted 7 May 2006

Alveolar surfactant modulates the antimicrobial function of bronchoalveolar macrophages (BAM). Little is known about the effect of surfactant-associated proteins in bronchoalveolar lavage fluid (BALF) on the interaction of BAM and Blastomyces dermatitidis. We investigated BALF enhancement or inhibition of TNF-{alpha} production by BAM stimulated by B. dermatitidis. BAM from CD-1 mice were stimulated with B. dermatitidis without or with normal BALF, surfactant protein A-deficient (SP-A–/–) or surfactant protein D-deficient (SP-D–/–) BALF, or a mixture of SP-A–/– and SP-D–/– BALF. An enzyme-linked immunosorbent assay was used to measure tumor necrosis factor alpha (TNF-{alpha}) in culture supernatants. BALFs were standardized in protein concentration. BAM plus B. dermatitidis (BAM-B. dermatitidis) TNF-{alpha} production was inhibited ≥47% by BALF or SP-A–/– BALF (at 290 or 580 µg of protein/ml, P < 0.05 to 0.01); in contrast, SP-D–/– BALF did not significantly inhibit TNF-{alpha} production. If SP-A–/– BALF was mixed in equal amounts with SP-D–/– BALF, TNF-{alpha} production by BAM-B. dermatitidis was inhibited (P < 0.01). Finally, pure SP-D added to SP-D–/– BALF inhibited TNF-{alpha} production by BAM-B. dermatitidis (P < 0.01). B. dermatitidis incubated with BALF and washed, plus BAM, stimulated 63% less production of TNF-{alpha} than did unwashed B. dermatitidis (P < 0.05). SP-D was detected by anti-SP-D antibody on BALF-treated unwashed B. dermatitidis in an immunofluorescence assay (IFA). The BALF depleted by a coating of B. dermatitidis lost the ability to inhibit TNF-{alpha} production (P < 0.05). 1,3-ß-Glucan was a good stimulator of BAM for TNF-{alpha} production and was detected on B. dermatitidis by IFA. ß-Glucan incubated with BALF inhibited the binding of SP-D in BALF to B. dermatitidis as demonstrated by IFA. Our data suggest that SP-D in BALF binds ß-glucan on B. dermatitidis, blocking BAM access to ß-glucan, thereby inhibiting TNF-{alpha} production. Thus, whereas BALF constituents commonly mediate antimicrobial activity, B. dermatitidis may utilize BALF constituents, such as SP-D, to blunt the host defensive reaction; this effect could reduce inflammation and tissue destruction but could also promote disease.

* Corresponding author. Mailing address: Department of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Ave., San Jose, CA 95128-2699. Phone: (408) 885-4313. Fax: (408) 885-4306. E-mail: stevens{at}stanford.edu.

Editor: A. Casadevall

Infection and Immunity, August 2006, p. 4549-4556, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.00243-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Koneti, A., Linke, M. J., Brummer, E., Stevens, D. A. (2008). Evasion of Innate Immune Responses: Evidence for Mannose Binding Lectin Inhibition of Tumor Necrosis Factor Alpha Production by Macrophages in Response to Blastomyces dermatitidis. Infect. Immun. 76: 994-1002 [Abstract] [Full Text]  
  • Baldan, A., Gomes, A. V., Ping, P., Edwards, P. A. (2008). Loss of ABCG1 Results in Chronic Pulmonary Inflammation. J. Immunol. 180: 3560-3568 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»