Identification of Human Macrophage Inflammatory Proteins 1α and 1β as a Native Secreted Heterodimer

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Abstract

Chemokines are secreted proteins that function as chemoattractants for leukocytes. The chemokines macrophage inflammatory protein 1α and 1β (MIP-1α and MIP-1β) now have been shown to be secreted from activated human monocytes and peripheral blood lymphocytes (PBLs) as a heterodimer. Immunoprecipitation and immunoblot analysis revealed that antibodies to either MIP-1α or MIP-1β precipitated a protein complex containing both MIP-1α and MIP-1β under normal conditions from culture supernatants and lysates of these cells. Mass spectrometry of the complexes, precipitated from the culture supernatants of monocytes and PBLs, revealed the presence of NH2-terminal truncated MIP-1α (residues 5-70) together with either intact MIP-1β or NH 2-terminal truncated MIP-1β (residues 3-69), respectively. The secreted MIP-1α/β heterodimers were dissociated into their component monomers under acidic conditions. Exposure of monocytes or PBLs to monensin induced the accumulation of heterodimers composed of NH2-terminal truncated MIP-1α and full-length MIP-1β in the Golgi complex. The mixing of recombinant chemokines in vitro demonstrated that heterodimerization of MIP-1α and MIP-1β is specific and that it occurs at physiological conditions, pH 7.4, and in the range of nanomolar concentrations. The data presented here provide the first biochemical evidence for the existence of chemokine heterodimers under natural conditions. Formation of heterodimers of MIP-α/β may have an impact on intracellular signaling events that contribute to CCR5 and possibly to other chemokine receptor functions.

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Guan, E., Wang, J., & Norcross, M. A. (2001). Identification of Human Macrophage Inflammatory Proteins 1α and 1β as a Native Secreted Heterodimer. Journal of Biological Chemistry, 276(15), 12404–12409. https://doi.org/10.1074/jbc.M006327200

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