Attenuation of spontaneous pseudopod formation in human neutrophils by pentoxifylline.
The effects of pentoxifylline (PTX) on spontaneous pseudopod formation in neutrophils in response to the tripeptide formyl-Met-Leu-Phe (fMLP), endotoxin, human complement C5a, and leukotriene B4 (LTB4) were examined in autologous plasma. Unseparated supernatant leukocyte suspensions from fresh heparinized venous human blood were incubated with PTX (0-5 mM) for 25 min and then stimulated for 5-25 min within a range of concentrations of fMLP, endotoxin, complement C5a, and LTB4. The cell suspensions were fixed with glutaraldehyde and stained with crystal violet in acetic acid; the percentage of neutrophils with pseudopods was determined under high-resolution light microscope. The results show that PTX significantly decreases formation of pseudopods in the presence of all four stimulators. The mechanism of pseudopod suppression appears to be independent of the adenosine receptor. PTX and its analogues, HWA 138 and HWA 448, decreased pseudopod formation by similar amounts when stimulated with 10(-8)M fMLP. These results suggest that PTX may improve microvascular perfusion and attenuate neutrophil-mediated injury by reducing the degree of neutrophil pseudopod formation in free suspension and microvascular entrapment.
Wong
P M
PM
Department of AMES-Bioengineering, University of California San Diego, La Jolla 92093-0412.
Schmid-Schönbein
G W
GW
D000199:Actins / Q000378:metabolism; D000328:Adult; D015936:Complement C5a / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010431:Pentoxifylline / Q000031:analogs & derivatives / Q000494:pharmacology*; D011554:Pseudopodia / Q000648:ultrastructure*; D011983:Receptors, Purinergic / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D000199:Actins; D004731:Endotoxins; D011983:Receptors, Purinergic; C062028:1-(5-hydroxy-5-methylhexyl)-3-methylxanthine; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; C061298:torbafylline; C031433:8-(4-sulfophenyl)theophylline; D015936:Complement C5a; D013806:Theophylline; D010431:Pentoxifylline