Overview
- Hu, J.Y. et al. (2001) J. Leukoc. Biol. 70, 155.
Alomone Labs MMK1 evokes a concentration-dependent rise in intracellular Ca2+ in non-differentiated HL-60 cells.Non-differentiated HL-60 cells were loaded with Fluo-3 AM. Changes in intracellular Ca2+ were detected via changes in Fluo-3 emission following agonist application. Application of MMK1 evoked a concentration-dependent rise in intracellular Ca2+. Normalized fluorescence before and after application (arrow) of control and of 1 nM, 10 nM ,100 nM and 1 µM MMK1 (as indicated).
Chemotactic factors from both Gram-positive and Gram-negative bacteria are short peptides with N-formyl methionine at the N-terminus (extensively reviewed in reference 1). These peptides are released from bacteria during infection and activate formyl peptide receptors (FPR), members of the G-protein coupled receptor (GPCR) superfamily. In humans, the FPR family consists mainly of three receptors, FPR1, FPR2/ALX (formerly FPRL1), and FPR3 (formerly FPRL2) which all couple to the Gi subtype of G-proteins and ultimately lead to the activation of phospholipase C and intracellular Ca2+ increase1,2.
MMK1 is a selective and potent agonist of the Formyl peptide receptor FPR23, which was originally derived from a random peptide library and was identified by a novel autocrine selection method in yeast engineered to express human FPR24.
FPR2 is expressed in the promyelocytic leukemia cell line HL-60 as well as in the chronic myelogenous leukemia cell line K5625. In human neutrophils, 1 µM MMK1 induces Ca2+ influx which is blocked by the specific FPR2 antagonist WRW46.
Resveratrol, a constituent of grape seeds, induces Ca2+ influx in human monocytes which is blocked by 10 µM MMK1, demonstrating that the inhibition of chemoattractant receptors contribute to the anti-inflammatory properties of resveratrol7.
