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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2011 ; 286
(6
): 4854-70
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus involves
binding of SP-A to the staphylococcal adhesin eap and the macrophage receptors
SP-A receptor 210 and scavenger receptor class A
#MMPMID21123169
Sever-Chroneos Z
; Krupa A
; Davis J
; Hasan M
; Yang CH
; Szeliga J
; Herrmann M
; Hussain M
; Geisbrecht BV
; Kobzik L
; Chroneos ZC
J Biol Chem
2011[Feb]; 286
(6
): 4854-70
PMID21123169
show ga
Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly
superinfection during viral influenza. The current study investigated the role of
surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous
studies showed that SP-A mediates phagocytosis via the SP-A receptor 210
(SP-R210). Here, we show that SP-R210 mediates binding and control of
SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus
through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage
uptake of Eap-expressing (Eap(+)) but not Eap-deficient (Eap(-)) S. aureus. In a
reciprocal fashion, SP-A failed to enhance uptake of Eap(+) S. aureus in
peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN))
blocking surface expression of SP-R210. Accordingly, WT mice cleared infection
with Eap(+) but succumbed to sublethal infection with Eap- S. aureus. However,
SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap(+) S.
aureus via the scavenger receptor scavenger receptor class A (SR-A), while
non-opsonic uptake of Eap(-) S. aureus was impaired. Macrophages express two
isoforms: SP-R210(L) and SP-R210(S). The results show that WT alveolar
macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-)
alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S).
Accordingly, SR-A(-/-) mice were highly susceptible to both Eap(+) and Eap(-) S.
aureus. The lungs of susceptible mice generated abnormal inflammatory responses
that were associated with impaired killing and persistence of S. aureus infection
in the lung. In conclusion, alveolar macrophage SP-R210(L) mediates recognition
and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory
responses and resolution of S. aureus pneumonia through interaction with SR-A.