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Comparison of biological responses of human monocytes and THP‐1 cells to chemokines of the intercrine‐ β family
Author(s) -
Vaddi Krishna,
Newton Robert C.
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.55.6.756
Subject(s) - chemokine , thp1 cell line , chemotaxis , monocyte , biology , stimulation , immunology , microbiology and biotechnology , cell culture , inflammation , endocrinology , receptor , biochemistry , genetics
The biological responses of human monocytes and cells of the monomyelocytic THP‐1 cell line to stimulation with members of the β chemokine family are described in this report. All three chemokines tested, MCP‐1, MIP‐l α , and RANTES, elicited mobilization of intracellular free calcium in monocytes and THP‐1 cells. The magnitude of response was highest with MCP‐1 stimulation. MCP‐1 desensitized monocyte responses to MIP‐l α and RANTES, but no such desensitization was observed in THP‐1 cells. MIP‐l α or RANTES did not desensitize either monocytes or THP‐1 cells to MCP‐1 stimulation. All three chemokines elicited a potent chemotactic response in monocytes that was comparable in magnitude to that of f‐Met‐Leu‐Phe. MIP‐l α and RANTES required a fivefold higher dose than MCP‐1 to elicit a peak response. On the contrary, THP‐1 cells showed no significant chemotactic response. Studies of the desensitization of the monocyte chemotactic response indicated that all three chemokines are capable of causing complete homologous desensitization. Heterologous desensitization was observed only when monocytes were treated with MCP‐1 followed by MIP‐l α or RANTES. Studies of actin polymerization and cell polarization responses of monocytes indicated that these two responses attained peak magnitude after 10 min of stimulation with any of the chemokines. Dose‐response kinetics were similar to those of the chemotactic response. THP‐1 cells again failed to show either of these two responses. Finally, the activation potential of the chemokines was measured by their ability to induce respiratory burst. A tenfold higher concentration than that causing peak chemotactic response was required to elicit respiratory burst and no heterologous desensitization was noticed. Respiratory burst could be induced in THP‐1 cells with a direct protein kinase C activator but not with any of the chemokines. These results indicate that, of the three examples tested, MCP‐1 is the most potent member of the β chemokine family in the biological responses examined. Although a calcium response was elicited in THP‐1 cells with chemokines, a lack of subsequent responses indicates some missing links in the downstream signal transduction pathways. J. Lcukoc. Biol . 55: 756–762; 1994.