Monocyte adherence induced by lipopolysaccharide involves CD14, LFA-1, and cytohesin-1. Regulation by rho and phosphatidylinositol 3-kinase

Zakaria Hmama, Keith L. Knutson, Patricia Herrera-Velit, Devki Nandan, Neil E. Reiner

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Mechanisms regulating lipopolysaccharide (LPS)-induced adherence to intercellular adhesion molecule (ICAM)-1 were examined using THP-1 cells transfected with CD14-cDNA (THP-1wt). THP-1wt adherence to ICAM-1 was LPS dose-related, time-dependent, and inhibited by antibodies to either CD14 or leukocyte function associated antigen (LFA)-1, but was independent of any change in the number of surface expressed LFA-1 molecules. A potential role for phosphatidylinositol (PI) 3-kinase (PI 3-kinase) in LPS-induced adherence was examined using the PI 3-kinase inhibitors LY294002 and Wortmannin. Both inhibitors selectively attenuated LPS-induced, but not phorbol 12-myristate 13-acetate-induced adherence. Inhibition by these agents was unrelated to any changes in either LPS binding to or LFA-1 expression by THP-1wt cells. LPS- induced adherence was also abrogated in U937 cells transfected with a dominant negative mutant of of PI 3-kinase. Toxin B from Clostridium difficile, an inhibitor of the Rho family of GTP-binding proteins, abrogated both PI-3 kinase activation and adherence induced by LPS. Cytohesin-1, a phosphatidylinositol 3,4,5-triphosphate-regulated adaptor molecule for LFA-1 activation, was found to be expressed in THP-1wt cells. In addition, treatment of THP1wt with cytohesin-1 antisense attenuated LPS-induced adherence. These findings suggest a model in which LPS induces adherence through a process of 'inside-out' signaling involving CD14, Rho, and PI 3- kinase. This converts low avidity LFA-1 into an active form capable of increased binding to ICAM-1. This change in LFA-1 appears to be cytohesin-1- dependent.

Original languageEnglish (US)
Pages (from-to)1050-1057
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number2
DOIs
StatePublished - Jan 8 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Monocyte adherence induced by lipopolysaccharide involves CD14, LFA-1, and cytohesin-1. Regulation by rho and phosphatidylinositol 3-kinase'. Together they form a unique fingerprint.

  • Cite this