Induction of monocyte expression of tumor necrosis factor α by the 30- kD α antigen of Mycobacterium tuberculosis and synergism with fibronectin

Htin Aung, Zahra Toossi, Jeffrey J. Wisnieski, Robert S. Wallis, Lloyd A. Culp, Nelson B. Phillips, Manijeh Phillips, Lynn E. Averill, Thomas M. Daniel, Jerrold J. Ellner

Research output: Contribution to journalArticlepeer-review

Abstract

Native 30-kD antigen, also known as α antigen, is a fibronectin- binding protein that is secreted by live Mycobacterium tuberculosis. This antigen may play an important biological role in the host-parasite interaction since it elicits delayed type hypersensitivity response and protective immunity in vivo and T lymphocyte blastogenesis and IFN-γ production in vitro. In the present study, we show that, TNF-α protein is produced in monocyte culture supernatants in response to 30-kD antigen and the level is as high as that to purified protein derivative of M. tuberculosis. This stimulatory effect was not due to contamination with either bacterial lipopolysaccharide or mycobacterial lipoarabinomannan. The preincubation of monocytes with plasma fibronectin significantly enhanced the release of TNF-α into the culture supernatants in response to 30-kD antigen. This effect was blocked by polyclonal antibody to plasma fibronectin. In contrast, the monocytic cell line U937 failed to release TNF-α protein in the culture supernatants in response to 30-kD antigen with or without preincubation with plasma fibronectin. To determine whether this observation was due to differential binding of the 30-kD to fibronectin on these cells, a cell based ELISA was used. Pretreatment of monocytes with fibronectin enhanced their binding of the 30-kD antigen U937 cells bound the 30-kD antigen weakly with or without fibronectin pretreatment. These results indicate that 30-kD antigen which is a known secretory antigen of M. tuberculosis is a stimulus for human monocytes to express TNF-α and that stimulatory effect may be mediated through plasma fibronectin.

Original languageEnglish (US)
Pages (from-to)1261-1268
Number of pages8
JournalJournal of Clinical Investigation
Volume98
Issue number5
StatePublished - Sep 1 1996
Externally publishedYes

Keywords

  • M. tuberculosis
  • monocytes
  • purified protein derivative
  • TNF-α
  • U937 cells

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Induction of monocyte expression of tumor necrosis factor α by the 30- kD α antigen of Mycobacterium tuberculosis and synergism with fibronectin'. Together they form a unique fingerprint.

Cite this