Low molecular weight heparin alters porcine neutrophil responses to platelet-activating factor.
Because platelet-activating factor (PAF) is an important mediator of inflammation and heparin has anti-inflammatory effects, we hypothesized that low molecular weight heparin (LMWH) would inhibit PAF-induced activation and chemotaxis in porcine neutrophils. Citrated blood was obtained from pentobarbital-anesthetized pigs, and neutrophils were isolated over a 55%/65% Percoll gradient. The effect of LMWH on basal phorbol myristate acetate (PMA)-induced superoxide (SO) release, as well as its effect on PAF priming for PMA-induced SO release, were investigated. Additionally, the effect of LMWH on PAF-induced chemotaxis of neutrophils across transwell membranes was evaluated. Baseline SO release in response to PMA was .351+/-.046 nmol/10(6) cells/min, and this was decreased to .289+/-.034 nmol/10(6) cells/min by pretreatment with 50 U/mL LMWH. PMA-induced SO production was increased by .240+/-.042 nmol/10(6) cells/min when cells were primed with 10 microM PAF. This priming effect of PAF was reduced significantly by pretreatment of neutrophils with LMWH at 10 and 50 U/mL. Chemotaxis of neutrophils in response to 100 microM PAF was significantly decreased to 70.02+/-6.4% (n = 8) of the control response by pretreatment of cells with 50 U/mL LMWH. We conclude that LMWH has anti-inflammatory effects on porcine neutrophils, which includes attenuation of cell activation and chemotaxis in response to the lipid-derived inflammatory mediator, PAF.
Kruse-Elliott
K T
KT
Department of Surgical Sciences, University of Wisconsin, Madison 53706, USA.
Chaban
K
K
Grossman
J E
JE
Tomasko
S
S
Kamke
C
C
Darien
B
B
D000818:Animals; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D008970:Molecular Weight; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010972:Platelet Activating Factor; D013481:Superoxides; D006493:Heparin; D013755:Tetradecanoylphorbol Acetate