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Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87).

Publication ,  Journal Article
Wong, WS; Simon, DI; Rosoff, PM; Rao, NK; Chapman, HA
Published in: Immunology
May 1996

Stimulation of monoblastic U937 cells with transforming growth factor beta 1 and 1,25-(OH)2 vitamin D3 (TGF-beta 1/D3) upregulates urokinase receptor (uPAR) and confers urokinase-dependent adhesiveness to the cells for serum- or vitronectin-coated surfaces. Recent studies show that uPAR itself is a high-affinity adhesion receptor for vitronectin and that urokinase (uPA) is an activator of this adhesive function. In the course of exploring possible G-protein involvement in this adhesion it was observed that TGF-beta 1/D3-primed U937 cells became adhesive to vitronectin in an uPAR-dependent manner when exposed to pertussis toxin (PTX). The adherent response is concentration- and time-dependent, and was not due to the ADP-ribosyltransferase activity of the toxin because the purified B-subunit of PTX was equally effective. Although promoting adhesion to serum- or vitronectin-coated surfaces, PTX blocked spontaneous cell adhesion to fibrinogen, an endogenous ligand for the Mac-1 receptor (CD11b/CD18). Flow cytometry study showed that expression of the alpha-subunit of Mac-1 (CD11b) on primed cells was increased by nearly threefold. Monoclonal antibody to CD11b abolished the PTX-induced cell adhesion and the binding of the primed cells to PTX-coated plates. Activation of Mac-1 receptor by its endogenous ligand fibrinogen induced cell adherent response similar to PTX. PTX, but not uPA, triggered a rapid rise in [Ca2+]i in primed U937 cells, and PTX-induced adhesion was significantly attenuated by 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy-methyl ester (BAPTA/AM), a selective membrane-permeant [Ca2+]i chelator. PTX-induced cell adhesion was also prevented by antibodies to uPAR and by conditioned medium containing soluble uPAR. Together these data indicate that PTX B-subunit may bind to Mac-1 integrin, which leads to a rapid rise in [Ca2+]i and subsequent activation of uPAR for adherence to vitronectin, suggesting a functional link between Mac-1 and activation of uPAR important to cellular trafficking and host defence in response to Bordetella pertussis infection.

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Published In

Immunology

DOI

ISSN

0019-2805

Publication Date

May 1996

Volume

88

Issue

1

Start / End Page

90 / 97

Location

England

Related Subject Headings

  • Vitronectin
  • Virulence Factors, Bordetella
  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Receptors, Urokinase Plasminogen Activator
  • Receptors, Cell Surface
  • Plasminogen Activators
  • Pertussis Toxin
  • Macrophage-1 Antigen
  • Leukemia, Myelomonocytic, Acute
 

Citation

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Wong, W. S., Simon, D. I., Rosoff, P. M., Rao, N. K., & Chapman, H. A. (1996). Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87). Immunology, 88(1), 90–97. https://doi.org/10.1046/j.1365-2567.1996.d01-646.x
Wong, W. S., D. I. Simon, P. M. Rosoff, N. K. Rao, and H. A. Chapman. “Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87).Immunology 88, no. 1 (May 1996): 90–97. https://doi.org/10.1046/j.1365-2567.1996.d01-646.x.
Wong WS, Simon DI, Rosoff PM, Rao NK, Chapman HA. Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87). Immunology. 1996 May;88(1):90–7.
Wong, W. S., et al. “Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87).Immunology, vol. 88, no. 1, May 1996, pp. 90–97. Pubmed, doi:10.1046/j.1365-2567.1996.d01-646.x.
Wong WS, Simon DI, Rosoff PM, Rao NK, Chapman HA. Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87). Immunology. 1996 May;88(1):90–97.

Published In

Immunology

DOI

ISSN

0019-2805

Publication Date

May 1996

Volume

88

Issue

1

Start / End Page

90 / 97

Location

England

Related Subject Headings

  • Vitronectin
  • Virulence Factors, Bordetella
  • Tumor Cells, Cultured
  • Transforming Growth Factor beta
  • Receptors, Urokinase Plasminogen Activator
  • Receptors, Cell Surface
  • Plasminogen Activators
  • Pertussis Toxin
  • Macrophage-1 Antigen
  • Leukemia, Myelomonocytic, Acute