Expression of the Interleukin-8 Receptors CXCR1 and CXCR2 on Cord-Blood-Derived Cultured Human Mast Cells

Abstract

Background: An increase in mast cell number at sites of inflamed tissues has been observed. However, the expression of CXC chemokine receptors on human mast cells is poorly understood. Methods: Cultured human mast cells were raised from human umbilical cord blood cells in the presence of stem cell factor and interleukin-6 (IL-6). The expression of surface chemokine receptors on the mast cells was analyzed by flow cytometry and that of mRNA was examined by the method of reverse transcriptase-polymerase chain reaction (RT-PCR). As functional assays for the receptors, mast cell migration was examined by a microchemotaxis assay and changes in the cytosolic free intracellular calcium concentrations ([Ca²⁺]_i) was measured using fura-2-loaded mast cells, respectively. Results: Expression of IL-8 receptors CXCR1 and CXCR2 was demonstrated by flow cytometry and of both mRNA by RT-PCR; however, CC chemokine receptors including CCR3 were not expressed on cord-blood-derived cultured human mast cells. IL-8 and its homologues showed chemotactic activity toward them in a dose-dependent manner, and IL-8 induced a dose-dependent rapid and transient increase in [Ca²⁺]_i in the mast cells. Conclusions: Our results suggest the surface expression of functional CXCR1 and CXCR2 on cord-blood-derived cultured human mast cells.

Monomeric IgE enhances human mast cell chemokine production: IL-4 augments and dexamethasone suppresses the response

“…Chemokines are thought to contribute to the pathogenesis of allergic disease by regulating the migration of the cells that orchestrate the inflammation associated with these disorders, including mast cells, [29][30][31][32] and it has been proposed that mast cell migration at such sites may be regulated, in part, by RANTES and IL-8. 33, 34 We have confirmed that our HUCBMCs express receptors that can bind IL-8-that is, the chemokine receptors, CXCR1 and CXCR2 (data not shown). Moreover, Inamura et al 34 reported the dose-dependent migration of HUCBMCs in response to as little as 1 ng/mL IL-8.…”

“…33, 34 We have confirmed that our HUCBMCs express receptors that can bind IL-8-that is, the chemokine receptors, CXCR1 and CXCR2 (data not shown). Moreover, Inamura et al 34 reported the dose-dependent migration of HUCBMCs in response to as little as 1 ng/mL IL-8.…”

CCR1-Mediated STAT3 Tyrosine Phosphorylation and CXCL8 Expression in THP-1 Macrophage-like Cells Involve Pertussis Toxin-Insensitive Gα14/16 Signaling and IL-6 Release

“…In human macrophages and macrophage-derived foam cells, CCL15 is capable of inducing the production of MMP-9 (27), whose expression is regulated by STAT3 (28), whereas CXCL8 is apparently involved in the recruitment of human NK cells to sites of early viral infection by mast cells (61) and metastasis of colon cancer (62). The release of CXCL8 activates CXCR2, which is coexpressed with CCR1 in macrophages (39) and human mast cells (63,64), leading to STAT3 Tyr 705 phosphorylation (65). Hence, the production of CXCL8 mediated by CCR1/Ga 14/16 may create another loop of STAT3 activation, which synergizes with the effect on CXCL8 secretion.…”

Low Molecular Weight CXCR2 Antagonists as Promising Therapeutics

“…CXCR2 is expressed on a broad range of leukocytes, including neutrophils, monocytes/macrophages, eosinophils, mast cells, basophils and lymphocytes [24][25][26][27][28]. The physiological function of CXCR2, however, has been most extensively studied in neutrophils.…”