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Medline® ID: 98226793
Citation: Kornbluth RS, Kee K, Richman DD, CD40 ligand (CD154) stimulation of macrophages to produce HIV-1-suppressive beta-chemokines., Proc Natl Acad Sci U S A 95: 9, 5205-10, Apr 28, 1998. Full Text Link COS Expertise Link
Address: Department of Medicine
University of California
San Diego
and Department of Veterans Affairs Medical Center
La Jolla
CA 92093
USA. rkornbluth@ucsd.edu
Abstract
beta-chemokines play an important role in the development of immunologic reactions. Macrophages are major beta-chemokine-producing cells during T-cell directed, delayed-type hypersensitivity reactions in tissues, and have been reported to be important producers of beta-chemokines in the lymph nodes of HIV-1-infected individuals. However, the physiological signals responsible for inducing macrophages to produce beta-chemokines have not been established. Two soluble T cell products, interferon-gamma and granulocyte-macrophage colony stimulating factor, were added to cultured macrophages, but failed to stimulate the production of macrophage inflammatory protein-1alpha and -1beta; regulated upon activation, normal T cell expressed and secreted (RANTES); or monocyte chemoattractant protein-1. Instead, direct cell-cell contact between macrophages and cells engineered to express CD40L (also known as CD154) resulted in the production of large amounts of macrophage inflammatory protein-1alpha and -1beta, and RANTES (all ligands for CCR5), and monocyte chemoattractant protein-1 (a ligand for CCR2). Supernatants from CD40L-stimulated macrophages protected CD4(+) T cells from infection by a nonsyncytium-inducing strain of HIV-1 (which uses CCR5 as a coreceptor). These results have implications for granulomatous diseases, and conditions such as atherosclerosis and multiple sclerosis, where CD40L-bearing cells have been found in the macrophage-rich lesions where beta-chemokines are being produced. Overall, these findings define a pathway linking the specific recognition of antigen by T cells to the production of beta-chemokines by macrophages. This pathway may play a role in anti-HIV-1 immunity and the development of immunologic reactions or lesions.
Type: JOURNAL ARTICLE
ISSN: 0027-8424
Language: Eng
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Grant number: RO1 AI35258\AI\NIAID
RO1 HL57911\HL\NHLBI
P30 CA23100-15S1\CA\NCI
+
CAS Registry/EC Number
0 (Chemokines, CC)
0 (Membrane Glycoproteins)
0 (Monocyte Chemoattractant Protein-1)
147205-72-9 (CD40L)
82115-62-6 (Interferon Type II)
83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
URL from COS to bookmark this record: http://medline.cos.com/cgi-bin/getRec?98226793
Medical Subject Headings (MeSH)
  • Cell Communication
  • Cell Membrane
    • Physiology
  • Cells, Cultured
  • Chemokines, CC *
    • Biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor
    • Pharmacology
  • Human
  • HIV-1 *
    • Growth and Development
  • Interferon Type II
    • Pharmacology
  • Macrophages *
    • Physiology
  • Membrane Glycoproteins *
    • Physiology
  • Monocyte Chemoattractant Protein-1
    • Biosynthesis
  • Support, U.S. Gov't, Non-P.H.S.
  • Support, U.S. Gov't, P.H.S.
  • T-Lymphocytes
    • Immunology
    • Virology
  • Virus Replication