In vivo recognition and clearance of red blood cells containing phosphatidylserine in their plasma membranes

A. J. Schroit, J. W. Madsen, Y. Tanaka

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310 Scopus citations


We have previously investigated the interaction of macrophages with red blood cells (RBC) displaying phosphatidylserine (PS) in their surface membranes after the transfer of the fluorescent lipid analog 1-acyl-2-[(N-4-nitrobenzo-2-oxa-1,3-diazole) aminocaproyl]phosphatidylserine to the RBC. This derivative, which is rapidly transferred to the RBC at 37°C, results in the efficient binding and phagocytosis of the RBC by autologous macrophages. In the present study, we show that 51Cr-labeled RBC containing [(N-4-nitrobenzo-2-oxa-1,3-diazole)aminododecanoyl]phosphatidylserine (NBD-PS) are rapidly cleared from the peripheral circulation of syngeneic mice and accumulate in the liver and spleen. Fluorescence microscopy of Kupffer cells and splenic macrophages isolated from the liver and spleens of these animals revealed phagocytosed fluorescent RBC, suggesting the clearance was probably due to endocytosis of the RBC. The accumulation of these RBC in the spleen was dramatic, with ~30% of the injected cells localizing in this organ within 60 min. In contrast, the intravenous injection of RBC containing similar amounts of NBD-phosphatidylcholine or NBD-phosphatidylglycerol did not result in clearance which differed significantly from control (untreated) RBC populations. The observed clearance of NBD-PS-containing RBC was much different than the clearance of opsonized RBC which preferentially localized in the liver. These findings show that PS in RBC can serve as a signal for triggering their in vivo recognition and concomitant elimination from the circulation and suggest that the exposure of endogenous PS in the outer leaflet or RBC which occurs in certain pathological conditions could trigger their removal from the circulation.

Original languageEnglish (US)
Pages (from-to)5131-5138
Number of pages8
JournalJournal of Biological Chemistry
Issue number8
StatePublished - 1985

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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