Regular Article
Substrate-Bound Fibronectin Enhances Scavenger Receptor Activity of Macrophages by Calcium Signaling

https://doi.org/10.1006/abbi.2001.2381Get rights and content

Abstract

We have previously found that ability of mouse macrophages to bind and take up oxidized low-density lipoprotein (oxLDL) through scavenger receptors is significantly enhanced when the cells are plated on fibronectin (FN)-coated culture substrates. Here, the mechanisms of the enhancement of the scavenger receptor activity by the substrate-bound FN was investigated using thioglycollate-induced mouse peritoneal macrophages. A Ca2+ channel blocker diltiazem and a calmodulin inhibitor W-7 reduced the scavenger receptor activity of the macrophages plated on FN-coated substrate to the level of the cells plated on uncoated substrate, as assessed by oxLDL binding, while the scavenger receptor activity of the macrophages on uncoated substrate was little affected. Similarly, FN-induced enhancement of the scavenger receptor activity assessed by oxLDL uptake was selectively inhibited by Ca2+ channel blockers (diltiazem, nifedipine, verapamil) and calmodulin inhibitors (W-7, trifluoperazine). Intracellular free Ca2+ level of the macrophages was increased, depending on extracellular Ca2+, when plated on FN-coated substrate. This increase in the Ca2+ level was inhibited by diltiazem and RGD-containing peptides present in cell adhesive region of FN. Like the substrate-bound FN, Ca2+ ionophore A23187 enhanced the scavenger receptor activity of binding and taking up of oxLDL. These results indicate that substrate-bound FN enhances scavenger receptor activity of macrophages by increasing channel-dependent Ca2+ influx. A microtubule disruptor, colchicine, and an actin filament disruptor, cytochalasin B, inhibited the FN-induced enhancement of the scavenger receptor activity, suggesting that these cytoskeletal structures are required for transmission of the adhesion signal of FN. The number of the scavenger receptors was found to increase by 1.4-fold upon adhesion signal of FN. We suggest that substrate-bound FN increases the number of the macrophage scavenger receptors as a result of induction of Ca2+ influx and causes increased accumulation of oxLDL within the cells, rendering the cells more susceptible to conversion into foam cells.

References (57)

  • H. Itabe et al.

    J. Biol. Chem.

    (1994)
  • A.M. Fogelman et al.

    J. Lipid Res.

    (1981)
  • S. Ishibashi et al.

    J. Biol. Chem.

    (1990)
  • B. Fuhrman et al.

    J. Lipid Res.

    (1991)
  • L.G. Fong et al.

    J. Biol. Chem.

    (1990)
  • H. Hsu et al.

    J. Biol. Chem.

    (1996)
  • L.A. Bottalico et al.

    J. Biol. Chem.

    (1991)
  • D.S. Leake et al.

    Biochim. Biophys. Acta

    (1989)
  • K.M. Yamada

    J. Biol. Chem.

    (1991)
  • M. Beppu et al.

    FEBS Lett.

    (1989)
  • O.H. Lowry et al.

    J. Biol. Chem.

    (1951)
  • R.O. Hynes

    Cell

    (1992)
  • M.A. Schwartz et al.

    J. Biol. Chem.

    (1994)
  • T. Fujimoto et al.

    J. Biol. Chem.

    (1991)
  • M.A. Schwartz et al.

    J. Biol. Chem.

    (1993)
  • M. Coppolino et al.

    J. Biol. Chem.

    (1995)
  • K. Burridge et al.

    Trend. Cell Biol.

    (1997)
  • N. Platt et al.

    Trend. Cell Biol.

    (1998)
  • S.S. Buys et al.

    Cell

    (1984)
  • S.S. Buys et al.

    J. Biol. Chem.

    (1987)
  • M. Beppu et al.

    FEBS Lett.

    (1991)
  • J. Rouleau et al.

    J. Am. Coll. Cardiol.

    (1983)
  • M.S. Brown et al.

    Annu. Rev. Biochem.

    (1981)
  • D. Steinberg et al.

    New Engl. J. Med.

    (1989)
  • J.L. Witztum et al.

    J. Clin. Invest.

    (1991)
  • M.E. Haberland et al.

    Science

    (1988)
  • S. Ylå-Herttuala et al.

    J. Clin. Invest.

    (1989)
  • W.J.S. de Viliers et al.

    J. Exp. Med.

    (1994)

    • Cited by (0)

    1

    To whom correspondence should be addressed. Fax: +81-426-76-4508. E-mail: [email protected].

    View full text
    Copyright © 2001 Academic Press. All rights reserved.