P Williams

Publications (2)8.5 Total impact

• Article: Interleukin-2 enhances angiogenesis and preserves cardiac function following myocardial infarction.

  M Bouchentouf, P Williams, K A Forner, J Cuerquis, V Michaud, P Paradis, E L Schiffrin, J Galipeau
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  ABSTRACT: We previously demonstrated that injection of IL-2-activated natural killer (NK) cells contribute to vascular remodeling via a4b7 integrin and killer cell lectin-like receptor (KLRG) 1 and promote cardiac repair following myocardial infarction (MI). The aim of the present study is to test the hypothesis that injection of recombinant human interleukin (rhIL)-2 improves angiogenesis and preserves heart function after MI. A single IV injection of rhIL-2 two days following MI improved by 27.7% the left ventricular (LV) fractional shortening of immune competent (C57Bl6) mice, but had no effect on cardiac function of immune-deficient (NOD-SCID IL2Rγnull) mice. Immunohistochemical analysis of C57Bl6 cross sections of heart revealed that collagen deposition was reduced by 23.1% and that capillary density was enhanced in the scar area and the border zone of the infarct respectively by 22.4% and 33.6% following rhIL-2 injection. In addition, rhIL-2 enhanced 1.6-fold the in vivo endothelial cell proliferation index and 1.8-fold the number of NK cell infiltrating the infarcted heart, but had no effect on the number of cardiac CD4 and CD8 cells. In vitro, rhIL-2 activated NK cells enhanced cardiac endothelial cell proliferation by 17.2%. Here we show that a single IV injection of rhIL-2 positively impacted cardiac function by improving angiogenesis through a process involving NK cells.
  Cytokine 12/2011; 56(3):732-8. · 3.02 Impact Factor
• Article: GMCSF-interleukin fusion cytokines induce novel immune effectors that can serve as biopharmaceuticals for treatment of autoimmunity and cancer.

  P Williams, J Galipeau
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  ABSTRACT: We created the GIFTs, fusions of granulocyte-colony macrophage-stimulating-factor with IL-2, or IL-15 or IL-21, in order to stimulate distinct, but complimentary elements of the immune response. We found that the physical coupling of two functionally distinct cytokines as a bifunctional hybrid allowed for synergistic bioactivity not seen by the simple combined use of parent components. Indeed, despite how these interleukins are pro-inflammatory cytokines that serve essential roles in the maturation of CD8(+) T cells and NK cells, the GIFTs were remarkably different from one another, with GIFT-2 and GIFT-21 promoting and GIFT-15 downregulating inflammation. The common denominator to the biochemistry of these fusokines was their ability to hijack the signalling machinery associated with common to their respective γ-chain interleukin receptors, radically altering the activation status of responding lymphomyeloid cells. By studying the GIFTs, we found that both secreted and cell surface factors presented by GIFT-activated lymphomyeloid cells were required to modulate the immune responses in murine models of multiple sclerosis and cancer. The ability of GIFTs to co-opt the normal signalling machinery of interleukin receptors leads to the acquisition of functional responder cell phenotypes unparalleled in nature. These novel properties provide opportunities to alter maladapted immune responses in health and disease.
  Journal of Internal Medicine 01/2011; 269(1):74-84. · 5.48 Impact Factor