PMID- 16861641 OWN - NLM STAT- MEDLINE DCOM- 20060829 LR - 20181113 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 74 IP - 8 DP - 2006 Aug TI - Effect of lung surfactant collectins on bronchoalveolar macrophage interaction with Blastomyces dermatitidis: inhibition of tumor necrosis factor alpha production by surfactant protein D. PG - 4549-56 AB - 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 > or = 47% by BALF or SP-A-/- BALF (at 290 or 580 microg 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-beta-Glucan was a good stimulator of BAM for TNF-alpha production and was detected on B. dermatitidis by IFA. beta-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 beta-glucan on B. dermatitidis, blocking BAM access to beta-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. FAU - Lekkala, Madhavi AU - Lekkala M AD - Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Ave., San Jose, California 95128-2699, USA. FAU - LeVine, Ann Marie AU - LeVine AM FAU - Linke, Michael J AU - Linke MJ FAU - Crouch, Erika C AU - Crouch EC FAU - Linders, Bruce AU - Linders B FAU - Brummer, Elmer AU - Brummer E FAU - Stevens, David A AU - Stevens DA LA - eng GR - P01 HL029594/HL/NHLBI NIH HHS/United States GR - R01 HL044015/HL/NHLBI NIH HHS/United States GR - HL-29594/HL/NHLBI NIH HHS/United States GR - HL-44015/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Pulmonary Surfactant-Associated Protein D) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (beta-Glucans) SB - IM MH - Animals MH - Blastomyces/immunology/*pathogenicity MH - Blastomycosis/immunology/microbiology MH - Bronchoalveolar Lavage Fluid/immunology/microbiology MH - Macrophage Activation MH - Macrophages, Alveolar/drug effects/*immunology MH - Male MH - Mice MH - Mice, Inbred C3H MH - Pulmonary Surfactant-Associated Protein D/deficiency/metabolism/*pharmacology MH - Tumor Necrosis Factor-alpha/*biosynthesis/*drug effects MH - beta-Glucans/metabolism PMC - PMC1539632 EDAT- 2006/07/25 09:00 MHDA- 2006/08/30 09:00 PMCR- 2006/12/01 CRDT- 2006/07/25 09:00 PHST- 2006/07/25 09:00 [pubmed] PHST- 2006/08/30 09:00 [medline] PHST- 2006/07/25 09:00 [entrez] PHST- 2006/12/01 00:00 [pmc-release] AID - 74/8/4549 [pii] AID - 0243-06 [pii] AID - 10.1128/IAI.00243-06 [doi] PST - ppublish SO - Infect Immun. 2006 Aug;74(8):4549-56. doi: 10.1128/IAI.00243-06.