Monocyte chemoattractant protein-1 gene is expressed in activated neutrophils and retinoic acid-induced human myeloid cell lines.
We have used differential display polymerase chain reaction to identify genes that are upregulated after retinoic acid (RA) treatment of human myeloblastic HL-60 cells. Three of the cDNAs cloned hybridized to RA-inducible transcripts on Northern blots, one of which was shown to encode sequences for monocyte chemoattractant protein-1 (MCP-1), a recently described cytokine that is chemotactic for monocytes but not for neutrophils. Nuclear run-on analysis indicated that the upregulation of the MCP-1 gene occurs at the transcriptional level in HL-60 cells. MCP-1 transcript levels also increased after RA treatment of the NB4 acute promyelocytic cell line. MCP-1 transcripts were undetectable in freshly isolated neutrophils by Northern analysis or reverse transcription-polymerase chain reaction but were readily detectable in neutrophils after incubation in media at 37 degrees C for 20 hours, suggesting that an activation event can lead to MCP-1 expression in neutrophils. Immunocytochemistry confirmed the presence of MCP-1 protein in activated neutrophils. This is the first report that the MCP-1 gene is RA-responsive in myeloid cell lines and is expressed in neutrophils. MCP-1 expression by activated neutrophils may play an important role in attracting monocytes to the site of tissue damage or infection.
Burn
T C
TC
Hematology/Oncology Division, Beth Israel Hospital, Boston, MA 02215.
Petrovick
M S
MS
Hohaus
S
S
Rollins
B J
BJ
Tenen
D G
DG
D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D014212:Tretinoin