In:
The Journal of Immunology, The American Association of Immunologists, Vol. 162, No. 12 ( 1999-06-15), p. 7335-7342
Abstract:
Taxol, a potent antitumor agent that binds β-tubulin and promotes microtubule assembly, results in mitotic arrest at the G2/M phase of the cell cycle. More recently, Taxol was shown to be a potent LPS mimetic in murine, but not in human macrophages, stimulating signaling pathways and gene expression indistinguishably from LPS. Although structurally unrelated to LPS, Taxol’s LPS-mimetic activities are blocked by inactive structural analogues of LPS, indicating that despite the species-restricted effects of Taxol, LPS and Taxol share a common receptor/signaling complex that might be important in LPS-induced human diseases. To identify components of the putatively shared Taxol/LPS receptor, a novel, photoactivatable Taxol analogue was employed to identify unique Taxol-binding proteins in murine macrophage membranes. Seven major Taxol-binding proteins, ranging from ∼50 to 200 kDa, were detected. Although photoactivatable Taxol analogue failed to bind to CD14, the prominent Taxol-binding protein was identified as CD18, the ∼96-kDa common component of the β2 integrin family. This finding was supported by the concomitant failure of macrophage membranes from Mac-1 knockout mice to express immunoreactive CD18 and the major Taxol-binding protein. In addition, Taxol-induced IL-12 p40 mRNA was markedly reduced in Mac-1 knockout macrophages and anti-Mac-1 Ab blocked secretion of IL-12 p70 in Taxol- and LPS-stimulated macrophages. Since CD18 has been described as a participant in LPS-induced binding and signal transduction, these data support the hypothesis that the interaction of murine CD18 with Taxol is involved in its proinflammatory activity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.162.12.7335
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
1999
detail.hit.zdb_id:
1475085-5
