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Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis.

Publication ,  Journal Article
Lillis, AP; Greenlee, MC; Mikhailenko, I; Pizzo, SV; Tenner, AJ; Strickland, DK; Bohlson, SS
Published in: J Immunol
July 1, 2008

C1q and members of the defense collagen family are pattern recognition molecules that bind to pathogens and apoptotic cells and trigger a rapid enhancement of phagocytic activity. Candidate phagocytic cell receptors responsible for the enhancement of phagocytosis by defense collagens have been proposed but not yet discerned. Engagement of phagocyte surface-associated calreticulin in complex with the large endocytic receptor, low-density lipoprotein receptor-related protein 1 (LRP/CD91), by defense collagens has been suggested as one mechanism governing enhanced ingestion of C1q-coated apoptotic cells. To investigate this possibility, macrophages were derived from transgenic mice genetically deficient in LRP resulting from tissue-specific loxP/Cre recombination. LRP-deficient macrophages were impaired in their ability to ingest beads coated with an LRP ligand when compared with LRP-expressing macrophages, confirming for the first time that LRP participates in phagocytosis. When LRP-deficient and -expressing macrophages were plated on C1q-coated slides, they demonstrated equivalently enhanced phagocytosis of sheep RBC suboptimally opsonized with IgG or complement, compared with cells plated on control protein. In addition, LRP-deficient and -expressing macrophages ingested equivalent numbers of apoptotic Jurkat cells in the presence and absence of serum. Both LRP-deficient and -expressing macrophages ingested fewer apoptotic cells when incubated in the presence of C1q-deficient serum compared with normal mouse serum, and the addition of purified C1q reconstituted uptake to control serum levels. These studies demonstrate a direct contribution of LRP to phagocytosis and indicate that LRP is not required for the C1q-triggered enhancement of phagocytosis, suggesting that other, still undefined, receptor(s) exist to mediate this important innate immune function.

Duke Scholars

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

July 1, 2008

Volume

181

Issue

1

Start / End Page

364 / 373

Location

United States

Related Subject Headings

  • Solubility
  • Phagocytosis
  • Mice, Knockout
  • Mice
  • Male
  • Macrophages
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Ligands
  • Immunology
  • Immunoglobulins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lillis, A. P., Greenlee, M. C., Mikhailenko, I., Pizzo, S. V., Tenner, A. J., Strickland, D. K., & Bohlson, S. S. (2008). Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. J Immunol, 181(1), 364–373. https://doi.org/10.4049/jimmunol.181.1.364
Lillis, Anna P., Mallary C. Greenlee, Irina Mikhailenko, Salvatore V. Pizzo, Andrea J. Tenner, Dudley K. Strickland, and Suzanne S. Bohlson. “Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis.J Immunol 181, no. 1 (July 1, 2008): 364–73. https://doi.org/10.4049/jimmunol.181.1.364.
Lillis AP, Greenlee MC, Mikhailenko I, Pizzo SV, Tenner AJ, Strickland DK, Bohlson SS. Murine low-density lipoprotein receptor-related protein 1 (LRP) is required for phagocytosis of targets bearing LRP ligands but is not required for C1q-triggered enhancement of phagocytosis. J Immunol. 2008 Jul 1;181(1):364–373.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

July 1, 2008

Volume

181

Issue

1

Start / End Page

364 / 373

Location

United States

Related Subject Headings

  • Solubility
  • Phagocytosis
  • Mice, Knockout
  • Mice
  • Male
  • Macrophages
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Ligands
  • Immunology
  • Immunoglobulins