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1996-02-26
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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).