The mannose-binding protein A region of glutamic acid185-alanine221 can functionally replace the surfactant protein A region of glutamic acid195-phenylalanine228 without loss of interaction with lipids and alveolar type II cells

Biochemistry
T HonmaT Akino

Abstract

Pulmonary surfactant protein A (SP-A) is a C-type lectin that regulates the uptake and secretion of surfactant lipids by alveolar type II cells and binds dipalmitoylphosphatidylcholine (DPPC) and galactosylceramide (GalCer). We isolated mannose-binding protein A (MBP-A) from rat sera, which is structurally analogous to SP-A, and examined if it was functionally equivalent to SP-A. We found that MBP-A did not possess the ability to interact with lipids and type II cells. The purpose of this study was to investigate the SP-A region involved in binding lipids and interacting with type II cells by using chimeric proteins with MBP-A. Chimeras AM1, AM2, and AM3 were constructed with SP-A/MBP splice junctions at Cys218/Gln210, Lys203/Cys195, and Gly194/Glu185, respectively. All of the chimeras bound DPPC and GalCer with activity comparable to recombinant SP-A. The three chimeras retained the ability to induce phospholipid vesicle aggregation and augment lipid uptake by type II cells, albeit to a lesser extent than wild type SP-A. The chimeras inhibited lipid secretion from type II cells with an IC50 of 0.5 microg/mL and competed effectively for SP-A receptor binding. In addition all these chimeras contained the epitope for monoclonal a...Continue Reading

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