HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Hypoxia inhibits macrophage migration.

Abstract
The chemokine monocyte chemoattractant protein (MCP)-1 plays a role in regulating the lymphocyte and macrophage infiltrate in ovarian cancer, but macrophages also accumulate in necrotic areas of the tumors where there is little MCP-1 expression (Negus, R. P. M. et al., Am. J. Pathol. 1997. 150: 1723-1734). Necrotic regions are likely to be hypoxic. In this study we show that hypoxia inhibits MCP-1-induced migration of THP-1 monocytic cells and human macrophages. In contrast, lymphocytes from peripheral blood migrate normally to an MCP-1 gradient in hypoxic conditions. The inhibition of monocyte migration by hypoxia is rapid and reversible. At the exposure times studied (30-90 min) hypoxia does not affect expression of the MCP-1 receptor CCR2B and cells exposed to hypoxia still respond to MCP-1 with an elevation of intracellular calcium. Although hypoxia is known to modulate gene expression, the inhibition of migration reported here was not due to the production of soluble factors, and mRNA expression of macrophage migration inhibitory factor was unchanged. Hypoxia-induced inhibition of chemotaxis was not limited to MCP-1. Hypoxia also inhibited the chemotactic response to macrophage inflammatory protein-1alpha, RANTES and the chemoattractant N-formyl-met-leu-phe, but hypoxic cells were still able to phagocytose opsonized red blood cells. We suggest that inhibition of migration by hypoxia is not due to gene regulation but is a reflection of metabolic changes in the cell. Transient hypoxia may regulate the distribution of macrophages in tumors and other inflammatory conditions.
AuthorsL Turner, C Scotton, R Negus, F Balkwill
JournalEuropean journal of immunology (Eur J Immunol) Vol. 29 Issue 7 Pg. 2280-7 (07 1999) ISSN: 0014-2980 [Print] Germany
PMID10427991 (Publication Type: Journal Article)
Chemical References
  • CCR2 protein, human
  • Chemokine CCL2
  • Macrophage Migration-Inhibitory Factors
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Cytokine
Topics
  • Cell Hypoxia (physiology)
  • Cell Line
  • Chemokine CCL2 (pharmacology, physiology)
  • Chemotaxis (drug effects, physiology)
  • Chemotaxis, Leukocyte (drug effects, physiology)
  • Female
  • Gene Expression
  • Humans
  • In Vitro Techniques
  • Macrophage Migration-Inhibitory Factors (biosynthesis)
  • Macrophages (drug effects, immunology, physiology)
  • Monocytes (drug effects, immunology, physiology)
  • Ovarian Neoplasms (immunology, pathology)
  • Phagocytosis
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Cytokine (genetics)
  • Signal Transduction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: