TY - JOUR
T1 - Effect of lung surfactant collectins on bronchoalveolar macrophage interaction with Blastomyces dermatitidis
T2 - Inhibition of tumor necrosis factor alpha production by surfactant protein D
AU - Lekkala, Madhavi
AU - LeVine, Ann Marie
AU - Linke, Michael J.
AU - Crouch, Erika C.
AU - Linders, Bruce
AU - Brummer, Elmer
AU - Stevens, David A.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/8
Y1 - 2006/8
N2 - 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-α 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-α) in culture supernatants. BALFs were standardized in protein concentration. BAM plus B. dermatitidis (BAM-B. dermatitidis) TNF-α 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-α production. If SP-A-/- BALF was mixed in equal amounts with SP-D -/- BALF, TNF-α production by BAM-B. dermatitidis was inhibited (P < 0.01). Finally, pure SP-D added to SP-D-/- BALF inhibited TNF-α production by BAM-B. dermatitidis (P < 0.01). B. dermatitidis incubated with BALF and washed, plus BAM, stimulated 63% less production of TNF-α 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-α production (P < 0.05). 1,3-β-Glucan was a good stimulator of BAM for TNF-α production and was detected on B. dermatitidis by IFA. β-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 β-glucan on B, dermatitidis, blocking BAM access to β-glucan, thereby inhibiting TNF-α production. Thus, whereas BALF constituents commonly mediate antimicrobial activity, B. dermatitidis may utilize BALF constituents, such as SP-D, to blent the host defensive reaction; this effect could reduce inflammation and tissue destruction but could also promote disease.
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-α 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-α) in culture supernatants. BALFs were standardized in protein concentration. BAM plus B. dermatitidis (BAM-B. dermatitidis) TNF-α 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-α production. If SP-A-/- BALF was mixed in equal amounts with SP-D -/- BALF, TNF-α production by BAM-B. dermatitidis was inhibited (P < 0.01). Finally, pure SP-D added to SP-D-/- BALF inhibited TNF-α production by BAM-B. dermatitidis (P < 0.01). B. dermatitidis incubated with BALF and washed, plus BAM, stimulated 63% less production of TNF-α 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-α production (P < 0.05). 1,3-β-Glucan was a good stimulator of BAM for TNF-α production and was detected on B. dermatitidis by IFA. β-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 β-glucan on B, dermatitidis, blocking BAM access to β-glucan, thereby inhibiting TNF-α production. Thus, whereas BALF constituents commonly mediate antimicrobial activity, B. dermatitidis may utilize BALF constituents, such as SP-D, to blent the host defensive reaction; this effect could reduce inflammation and tissue destruction but could also promote disease.
UR - http://www.scopus.com/inward/record.url?scp=33746659837&partnerID=8YFLogxK
U2 - 10.1128/IAI.00243-06
DO - 10.1128/IAI.00243-06
M3 - Article
C2 - 16861641
AN - SCOPUS:33746659837
VL - 74
SP - 4549
EP - 4556
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 8
ER -