The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8 - PubMed (original) (raw)

Figure 1

Calcium flux of CCR8-Y3 and CCR5-293 cells in response to various chemokines. (A) Various chemokines were used at concentrations ranging from 10 to 50 nM to induce a calcium flux in Y3-CCR8 cells. Chemokines tested included MCP-1, MCP-2, MCP-3, MCP-4, mMCP-5, eotaxin, MIP-1α, MIP-1β, DC-CK-1, RANTES, HCC-1, mMIP-1γ, m6Ckine, BCA-1, MIP-3α, MIP-3β, 6Ckine, fractalkine (soluble domain), TARC, MDC, MIP-4, mC10, I-309, TECK, Mig, IP-10, vMIP-I, SDF-1α, SDF-1β, IL-8, mJE, Gro-α, ENA-78, mTECK, mLptn, NAP-2, mGCP-2, mLIX, and mMIP-2. Only positive responses are shown as calcium flux (units) versus time and a vehicle control is indicated. (B) Dose–response of CCR8-Y3 cells to vMIP-I. CCR8-Y3 cells were stimulated with vMIP-I in a range of 1 μM–100 pM. A vehicle control is indicated. Each curve shown is the average of duplicate wells for each dose (SD did not exceed 10% of peak height). (C) Dose-dependent heterologous desensitization of I-309/vMIP-I signaling. CCR8-Y3 cells were exposed to increasing concentrations of an initial agonist, either I-309 (□) or vMIP-I (○), for 3 min before a second stimulation with the indicated chemokine at 10 nM. Preincubation in vehicle alone is indicated (vehicle/I-309, •; vehicle/vMIP-I, ▪). Results are graphed as peak response versus concentration of initial agonist. (D) The response of CCR5-293 cells to a panel of chemokines. The peak response of CCR5-293 cells to various chemokines is shown. The panel used was identical to that used in A except for the addition of 100 nM RANTES. In addition, vMIP-I was tested at 1 μM, 100 nM, and 10 nM. Only those chemokines producing a response and a few selected negative controls are shown.