Chemokines induced by infection of mononuclear phagocytes with mycobacteria and present in lung alveoli during active pulmonary tuberculosis

Am J Respir Cell Mol Biol. 1998 Sep;19(3):513-21. doi: 10.1165/ajrcmb.19.3.2815.


The capacity of Mycobacterium tuberculosis (MTB) to induce production of chemokines with known chemotactic activity for monocytes and lymphocytes, the cellular building blocks of granulomas, was investigated. These chemokines included regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1alpha (MIP-1alpha). MTB stimulated production of MCP-1 and MIP-1alpha by blood monocytes (MN) and alveolar macrophages (AM). MTB infection of MN and AM stimulated release but not production of RANTES. AM produced or released significantly higher levels than MN of RANTES (by 2.1-fold), MCP-1 (by 6.9-fold), and MIP-1alpha (by 5. 5-fold) (P < 0.05 for each). This study also confirmed that MTB-infected AM produce the chemokine interleukin (IL)-8. MTB infection of AM resulted in increased steady-state expression of messenger RNA (mRNA) for MCP-1 and MIP-1alpha and minimal increased expression of RANTES mRNA. Both an avirulent (H37Ra) and a virulent (H37Rv) strain of MTB and purified protein derivative of H37Rv but not latex beads induced production of chemokines. Supernatants of MTB-infected cells demonstrated chemotactic activity for both monocytes and lymphocytes partially inhibitable by neutralizing antibodies against the chemokines studied. Bronchoalveolar lavage fluid from patients with active pulmonary tuberculosis as compared with healthy control subjects contained increased levels of RANTES (by 8-fold), MCP-1 (by 2.7-fold), and IL-8 (by 8.9-fold) (P < 0.05), but not MIP-1alpha, as compared with healthy control subjects. Thus, multiple chemokines may be involved in recruitment of cells for granuloma formation in tuberculosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies / pharmacology
  • Bronchoalveolar Lavage Fluid / cytology*
  • Cell Movement / physiology
  • Chemokine CCL2 / metabolism
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / metabolism
  • Chemokines / metabolism*
  • Humans
  • Interleukin-8 / metabolism
  • Macrophage Inflammatory Proteins / pharmacology
  • Macrophages, Alveolar / metabolism*
  • Macrophages, Alveolar / microbiology
  • Monocytes / metabolism*
  • Monocytes / microbiology
  • Mycobacterium tuberculosis / pathogenicity*
  • RNA, Messenger / metabolism
  • Tuberculosis / physiopathology


  • Antibodies
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines
  • Interleukin-8
  • Macrophage Inflammatory Proteins
  • RNA, Messenger