The signals that a cell receives from its environment can be altered if cells acquire new receptors on their cell surface. In fact, cells appear to be able to acquire receptors that they themselves are not programmed to express through incorporation of membrane-derived microparticles released from other cells. In particular, during inflammatory responses, platelet-derived microparticles (PMPs) are released that can transfer molecules to cells in the blood vessel walls or to cells in the blood, like neutrophils. Salanova et al. discovered that the integrin glycoprotein IIb/IIIa (GPIIb/IIIa), which recognizes various adhesion proteins and thus contributes to platelet aggregation, can be transferred in PMPs to circulating neutrophils. After treatment of whole human blood with adenosine diphosphate to activate platelets, the authors used flow cytometry and fluorescence microscopy to show that neutrophils, which originally showed little evidence of GPIIb/IIIa on their cell surface, acquired small patches on the cell surface that contained the integrin. These receptors appeared to be transferred by PMPs, because they were also present when PMPs were isolated and then applied to purified neutrophils. Neutrophils activate the transcription factor NF-κB when they receive integrin signals together with stimulation by cytokines. Salanova et al. observed that neutrophils treated with the cytokine GM-CSF (granulocyte-macrophage colony-stimulating factor) that had also acquired GPIIb/IIIa from PMPs activated NF-κB in response to antibodies that stimulated GPIIb/IIIa or the native integrin CD18. Blocking activation of either one of the integrins inhibited activation of NF-κB. Similarly treated cells that didn’t acquire PMPs did not activate NF-κB in response to activation of either integrin. Fluorescence microscopy indicated that the two integrins were localized together on the cell surface of the neutrophils. Thus, transferred GPIIb/IIIa appears to act together with native integrins of the neutrophil. Inflammation is thought to contribute to the deleterious effects of vascular injury, and inhibition of such responses may be of therapeutic value. In this regard, Salanova et al. showed that inhibitors of GPIIb/IIIa already in use clinically to limit platelet aggregation prevented activation of NF-κB in neutrophils that had acquired GPIIb/IIIa and were exposed to GM-CSF and fibronectin (an integrin ligand).
B. Salanova, M. Choi, S. Rolle, M. Wellner, F. C. Luft, R. Kettritz, β2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-κB activation of human neutrophils. J. Biol Chem. 282, 27960-27969 (2007). [Abstract] [Full Text]