title: Heat shock protein 27 inhibits apoptosis in human neutrophils.
abstract: BACKGROUND
  Prolonged neutrophil(PMN) survival has been implicated in tissue injury following sepsis. A variety of bacterial products have been identified which inhibit PMN apoptosis including lipopolysaccharide(LPS). Extracellular heat shock proteins(Hsp) have recently been identified as potent regulatory signals for the innate immune system during the inflammatory response. We hypothesized that Hsp 27 can affect PMN phenotype with respect to apoptosis and cytokine profile.
  
  
  METHODS
  PMN were isolated from the peripheral blood of healthy human volunteers by red blood cell sedimentation and gradient centrifugation. Cells were placed in media and cultured for 18 h with and without recombinant human Hsp 27 at various concentrations. In parallel experiments, PMN were stimulated with LPS, a known inhibitor of PMN apoptosis, for comparison. Apoptosis was quantified using annexin V and propidium iodide staining with flow cytometric analysis. Culture supernatants were assayed for secretion of TNF-alpha, IL-10, and IL-12.
  
  
  RESULTS
  Hsp 27 significantly inhibits PMN apoptosis [control; 81.8 +/- 3.6%, vs Hsp 27, 60.4 +/- 4.1% p < 0.05]. The reduction is similar to that signaled by LPS, alone. Together their effect is not synergistic. The Hsp 27 response is dose-dependent. Hsp 27 does not induce secretion of TNF-alpha, IL-10, or IL-12, whereas LPS does signal IL-12 and TNF-alpha secretion.
  
  
  CONCLUSIONS
  These data demonstrate that exogenous Hsp 27 may play a role in neutrophil-mediated tissue injury during trauma and sepsis via its ability to inhibit neutrophil apoptosis. However, Hsp 27 does not significantly alter neutrophil phenotype with respect to cytokine production profile.
authors: Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts, 01655, USA.
authors: K
authors: K
authors: Sheth
authors: A
authors: A
authors: De
authors: B
authors: B
authors: Nolan
authors: J
authors: J
authors: Friel
authors: A
authors: A
authors: Duffy
authors: R
authors: R
authors: Ricciardi
authors: C
authors: C
authors: Miller-Graziano
authors: P
authors: P
authors: Bankey
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D009994:Osmolar Concentration; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006360:Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12