       Document 0532
 DOCN  M9620532
 TI    The role of monocyte chemotactic protein-1 (MCP-1) in the recruitment of
       monocytes and CD4+ T cells during a pulmonary Cryptococcus neoformans
       infection.
 DT    9602
 AU    Huffnagle GB; Strieter RM; Standiford TJ; McDonald RA; Burdick MD;
       Kunkel SL; Toews GB; Internal Medicine-Pulmonary and Critical Care
       Medicine Division,; University of Michigan Medical Center, Ann Arbor
       48109, USA.
 SO    J Immunol. 1995 Nov 15;155(10):4790-7. Unique Identifier : AIDSLINE
       MED/96062297
 AB    Cryptococcus neoformans is acquired via the respiratory tract and is the
       leading cause of fatal mycosis in AIDS. Development of a T cell-mediated
       pulmonary inflammatory response is critical for clearance of this
       pathogen; however, the chemotactic factors that mediate inflammatory
       cell recruitment into the lungs have not been identified. In the present
       study, the bronchoalveolar lavage (BAL) fluid levels of the C-C
       chemokine monocyte chemotactic protein-1 (MCP-1) and the recruitment of
       inflammatory cells both increased following pulmonary infection with C.
       neoformans. The kinetics of MCP-1 production in the lungs correlated
       most closely with the recruitment of CD4+ T cells and
       monocytes/macrophages. Administration of neutralizing anti-MCP-1 Abs in
       vivo reduced the BAL fluid levels of MCP-1, decreased the recruitment of
       both macrophages (> 95%) and CD4+ T cells (76 +/- 9%), and inhibited
       cryptococcal clearance. Although no in vitro neutrophil or B cell
       chemotactic activity has been reported for MCP-1, recruitment of these
       leukocytes was also decreased in anti-MCP-1-treated mice (most likely an
       indirect effect of reducing the number of CD4+ T cells and macrophages).
       Neutralization of MCP-1 also resulted in decreased BAL fluid levels of
       TNF-alpha and IL-6. This is the first demonstration of a role for MCP-1
       in clearance of an infection, and provides direct evidence that MCP-1
       plays a critical role in the T cell-dependent immune response to C.
       neoformans.
 DE    Animal  Bronchoalveolar Lavage  Chemotaxis
       Cryptococcosis/*IMMUNOLOGY/PATHOLOGY  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY/PATHOLOGY  Female  Immunity, Cellular  Lung
       Diseases, Fungal/*IMMUNOLOGY/MICROBIOLOGY/PATHOLOGY  Mice  Mice, Inbred
       CBA  Monocyte Chemoattractant Protein-1/*IMMUNOLOGY
       Monocytes/*IMMUNOLOGY/PATHOLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

