Enhancement of monocyte transendothelial migration by granulocyte-macrophage colony-stimulating factor: requirement for chemoattractant and CD11a/CD18 mechanisms.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances and primes monocyte functions, but its role in monocyte migration is poorly understood. We examined monocyte migration across human umbilical vein endothelial cells (HUVEC) grown on filters. GM-CSF had no chemotactic or chemokinetic effect. However, GM-CSF enhanced monocyte transendothelial migration (TEM) through unstimulated and IL-1-activated (5 h) HUVEC in response to C5a or monocyte chemoattractant protein-1 in a dose-dependent fashion, increasing the migration from 28.7 +/- 5.3% to 41.8 +/- 6.2% (n = 8, p < 0.05) and from 34.8 +/- 6% to 50.3 +/- 3.1%, p < 0.05), respectively. The enhanced TEM was inhibited by monoclonal antibodies (mAb) to LFA-1, but not by mAb to Mac-1 or to VLA-4. Furthermore, GM-CSF up-regulated and activated LFA-1, as assessed by NKI-L16 neoepitope expression. The results indicate that: (1) GM-CSF can prime monocytes for increased TEM, (2) GM-CSF enhances LFA-1-mediated monocyte TEM and (3) this effect is in part mediated by increasing LFA-1 expression and activation. Thus, increased GM-CSF production may promote monocyte accumulation in inflammation not only by inducing monocytosis, but also enhancing migration.
Shang
X Z
XZ
Department of Pediatrics, Dalhousie University, Halifax, Canada.
Issekutz
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AC
D018821:CD18 Antigens / Q000276:immunology*; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000276:immunology / Q000494:pharmacology; D002630:Chemotactic Factors / Q000276:immunology / Q000494:pharmacology; D015936:Complement C5a / Q000276:immunology / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology
D018821:CD18 Antigens; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D019012:Integrin beta1; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D015936:Complement C5a; D016178:Granulocyte-Macrophage Colony-Stimulating Factor