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Ligation of low-density lipoprotein receptor-related protein with antibodies elevates intracellular calcium and inositol 1,4, 5-trisphosphate in macrophages.

Publication ,  Journal Article
Misra, UK; Gawdi, G; Pizzo, SV
Published in: Arch Biochem Biophys
December 15, 1999

We have probed the signaling characteristics of the macrophage low-density lipoprotein receptor-related protein (LRP) with monoclonal antibody 8G1, its Fab and F(ab')(2) fragments directed against the ligand binding heavy chain, and monoclonal antibody 5A6 directed against the membrane-spanning light chain of LRP. Ligation of LRP with 8G1, its Fab and F(ab')(2) fragments, or 5A6 increased intracellular Ca(2+) levels two- to threefold. Prior ligation of LRP with 8G1 did not affect the increase in [Ca(2+)](i) observed on subsequent ligation of LRP with lactoferrin, P. exotoxin A, or lipoprotein lipase. Binding to LRP by 8G1, its Fab and F(ab')(2) fragments, or 5A6 increased inositol 1,4,5-trisphosphate (IP(3)) levels by 50 to 100%. Incubation of macrophages with guanosine 5', 3'-O(thio)-triphosphate (GTP-gamma-S) before treatment with antibody potentiated and sustained the 8G1-induced increase in IP(3) levels. Treatment of macrophages with guanyl-5'-yl thiophosphate prior to GTP-gamma-S treatment abolished the GTP-gamma-S-potentiated increase in IP(3) levels in 8G1-treated macrophages. Antibody-induced increases in IP(3) and [Ca(2+)](i) in macrophages on ligation of LRP were pertussis toxin sensitive. Binding of 8G1 or its Fab or F(ab')(2) fragments to LRP stimulated macrophage protein kinase C (PKC) activity as evaluated by histone IIIs phosphorylation by about two- to sevenfold. Staurosporin inhibited the anti-LRP antibody-induced increase in PKC activity. Ligation of LRP with 8G1 increased cellular cAMP levels about twofold. Preincubation of macrophage with the LRP-binding protein receptor-associated protein suppressed the 8G1-induced increase in cAMP levels. Thus, binding of antibodies directed against either chain of LRP triggers complex signaling cascades.

Duke Scholars

Published In

Arch Biochem Biophys

DOI

ISSN

0003-9861

Publication Date

December 15, 1999

Volume

372

Issue

2

Start / End Page

238 / 247

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Virulence Factors
  • Second Messenger Systems
  • Receptors, LDL
  • Pseudomonas aeruginosa Exotoxin A
  • Protein Kinase C
  • Phosphorylation
  • Pertussis Toxin
  • Mice, Inbred C57BL
  • Mice
 

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Misra, U. K., Gawdi, G., & Pizzo, S. V. (1999). Ligation of low-density lipoprotein receptor-related protein with antibodies elevates intracellular calcium and inositol 1,4, 5-trisphosphate in macrophages. Arch Biochem Biophys, 372(2), 238–247. https://doi.org/10.1006/abbi.1999.1521
Misra, U. K., G. Gawdi, and S. V. Pizzo. “Ligation of low-density lipoprotein receptor-related protein with antibodies elevates intracellular calcium and inositol 1,4, 5-trisphosphate in macrophages.Arch Biochem Biophys 372, no. 2 (December 15, 1999): 238–47. https://doi.org/10.1006/abbi.1999.1521.
Misra, U. K., et al. “Ligation of low-density lipoprotein receptor-related protein with antibodies elevates intracellular calcium and inositol 1,4, 5-trisphosphate in macrophages.Arch Biochem Biophys, vol. 372, no. 2, Dec. 1999, pp. 238–47. Pubmed, doi:10.1006/abbi.1999.1521.
Journal cover image

Published In

Arch Biochem Biophys

DOI

ISSN

0003-9861

Publication Date

December 15, 1999

Volume

372

Issue

2

Start / End Page

238 / 247

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Virulence Factors
  • Second Messenger Systems
  • Receptors, LDL
  • Pseudomonas aeruginosa Exotoxin A
  • Protein Kinase C
  • Phosphorylation
  • Pertussis Toxin
  • Mice, Inbred C57BL
  • Mice