Neutrophil degranulation and the effects of phosphodiesterase inhibition.
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.
Deree
Jessica
J
Division of Trauma and Surgical Critical Care, Department of Surgery, University of California San Diego School of Medicine, San Diego, CA, USA.
Lall
Rohan
R
Melbostad
Heidi
H
Grant
Michael
M
Hoyt
David B
DB
Coimbra
Raul
R
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
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