title: Neutrophil degranulation and the effects of phosphodiesterase inhibition.
abstract: BACKGROUND
  Neutrophils play a major role as the first line in host defense after exposure to bacterial products. However, an exaggerated inflammatory response characterized by overwhelming neutrophil activation can be injurious to the host. Pentoxifylline (PTX), a nonspecific phosphodiesterase inhibitor, has been shown to attenuate neutrophil oxidative burst and decrease proinflammatory mediator synthesis. We hypothesized that PTX down-regulates neutrophil activation by decreasing the surface expression of both CD35 and CD66b, two markers of neutrophil degranulation.
  
  
  METHODS
  Venous blood was obtained from three healthy volunteers. Whole blood was incubated with HBSS (control), f-methionyl-leucyl-phenylalanine (fMLP, 1 microM/L), PTX (2 mM/L), or fMLP + PTX. CD35 and CD66b expression were measured by flow cytometry.
  
  
  RESULTS
  fMLP treatment caused a significant increase in CD35 and CD66b expression of when compared to controls (P < 0.01). PTX treatment revealed expression of both markers comparable to the control group. A 38% decrease in CD35 (64 +/- 12 versus 100; P < 0.01) and a 52% decrease in CD66b (48 +/- 7 versus 100; P < 0.01) expression were demonstrated in the fMLP + PTX group when compared to fMLP alone.
  
  
  CONCLUSIONS
  In addition to the known effects of PTX on neutrophil oxidative burst, PTX also affects neutrophil degranulation, an essential step in enzyme release and subsequent tissue injury. These findings may have clinical relevance in the treatment of disease processes due to inflammation in which primed neutrophils play a role.
authors.affiliation: Division of Trauma and Surgical Critical Care, Department of Surgery, University of California San Diego School of Medicine, San Diego, CA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Deree
authors.forename: Rohan
authors.initials: R
authors.lastname: Lall
authors.forename: Heidi
authors.initials: H
authors.lastname: Melbostad
authors.forename: Michael
authors.initials: M
authors.lastname: Grant
authors.forename: David B
authors.initials: DB
authors.lastname: Hoyt
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D015536:Down-Regulation; D058851:GPI-Linked Proteins; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D017463:Receptors, Complement 3b / Q000378:metabolism; D022142:Secretory Vesicles / Q000187:drug effects
chemical_list: D015703:Antigens, CD; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D010726:Phosphodiesterase Inhibitors; D017463:Receptors, Complement 3b; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010431:Pentoxifylline