RGD Reference Report - Potential role of monocyte chemoattractant protein 1/JE in monocyte/macrophage-dependent IgA immune complex alveolitis in the rat. - Rat Genome Database

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Potential role of monocyte chemoattractant protein 1/JE in monocyte/macrophage-dependent IgA immune complex alveolitis in the rat.

Authors: Jones, ML  Mulligan, MS  Flory, CM  Ward, PA  Warren, JS 
Citation: Jones ML, etal., J Immunol. 1992 Sep 15;149(6):2147-54.
RGD ID: 8549558
Pubmed: PMID:1387671   (View Abstract at PubMed)

We have examined the role of monocyte chemoattractant protein 1 (MCP 1) in the pathogenesis of monocyte/macrophage-dependent IgA immune complex alveolitis in the rat. Rat MCP 1 was cloned and expressed in order to facilitate analysis of its function in rat models of human disease. A cDNA library was constructed from rat pulmonary artery endothelial cells stimulated with TNF-alpha. The cDNA library was screened with synthetic oligonucleotide probes based on the recently published rat MCP 1 cDNA sequence. Among numerous MCP 1-positive clones, four full length (approximately 480 bp) cDNA were rescued, amplified by polymerase chain reaction, and ligated into a pJVETLZ baculovirus transfer vector. Spodoptera frugiperda insect cells (Sf-21) infected with baculovirus recombinants (Auto-grapha california nuclear polyhedrosis virus) bearing properly oriented MCP 1 cDNA (AcMCP 1) directed the expression of unique peptides of 18, 21, and 23 kDa. Treatment of AcMCP 1-infected Sf-21 cells with tunicamycin resulted in reduced production of the 21- and 23-kDa proteins and an increase in 16- to 18-kDa products, the predicted size range of uncleaved and nonglycosylated rat MCP 1. Denatured and refolded 23-kDa and 21-kDa rat MCP 1 species exhibited dose-dependent monocyte-specific chemotactic activity at concentrations as low as 10(-10) M whereas the 18-kDa species exhibited negligible activity. Antibodies that react with the immunoblot, block rat rMCP 1-directed monocyte chemotaxis, and neutralize monocyte-specific chemotactic activity secreted by TNF-stimulated rat endothelial cells were raised in rabbits immunized with the 23-kDa MCP 1 species. Intravenous administration of anti-MCP 1 antibodies upon initiation of IgA immune complex lung injury resulted in a marked reduction in lung injury as measured by pulmonary vascular permeability, alveolar hemorrhage, and pulmonary monocyte/macrophage recruitment and pulmonary monocyte/macrophage recruitment. These data suggest that MCP 1 may play an important role in the pathogenesis of monocyte/macrophage-dependent IgA immune complex alveolitis in the rat.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
interstitial lung disease treatmentISOCcl2 (Rattus norvegicus)8549558; 8549558 RGD 
interstitial lung disease treatmentIMP 8549558 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of monocyte chemotaxis  IDA 8549558 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)


Additional Information