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10.1074/jbc.M110.125567

http://scihub22266oqcxt.onion/10.1074/jbc.M110.125567
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C3039347!3039347 !21123169
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suck abstract from ncbi


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pmid21123169
      J+Biol+Chem 2011 ; 286 (6 ): 4854-70
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  • 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.
  • |Adhesins, Bacterial/genetics/*metabolism [MESH]
  • |Animals [MESH]
  • |COS Cells [MESH]
  • |Chlorocebus aethiops [MESH]
  • |Humans [MESH]
  • |Lung/metabolism [MESH]
  • |Macrophages, Alveolar/*metabolism [MESH]
  • |Macrophages, Peritoneal/*metabolism [MESH]
  • |Mice [MESH]
  • |Mice, Knockout [MESH]
  • |Phagocytosis/physiology [MESH]
  • |Pneumonia, Staphylococcal/genetics/*metabolism [MESH]
  • |Pulmonary Surfactant-Associated Protein A/genetics/*metabolism [MESH]
  • |Receptors, Cell Surface/genetics/*metabolism [MESH]


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