LOW-MOLECULAR-WEIGHT HEPARIN ALTERS PORCINE NEUTROPHIL RESPONSES TO PLATELET-ACTIVATING-FACTOR

Because platelet-activating factor (PAF) is an important mediator of i nflammation and heparin has anti-inflammatory effects, we hypothesized that low molecular weight heparin (LMWH) would inhibit PAF-induced ac tivation and chemotaxis in porcine neutrophils. Citrated blood was obt ained from pentobarbital-anesthetized pigs, and neutrophils were isola ted over a 55%/65% Percoll gradient. The effect of LMWH on basal phorb ol myristate acetate (PMA)-induced superoxide (SO) release, as well as its effect on PAF priming for PMA-induced SO release, were investigat ed. Additionally, the effect of LMWH on PAF-induced chemotaxis of neut rophils across transwell membranes was evaluated. Baseline SO release in response to PMA was .351 +/- .046 nmol/10(6) cells/min, and this wa s decreased to .289 +/- .034 nmol/10(6) cells/min by pretreatment with 50 U/mL LMWH. PMA-induced SO production was increased by .240 +/- .04 2 nmol/10(6) cells/min when cells were primed with 10 mu M PAF. This p riming effect of PAF was reduced significantly by pretreatment of neut rophils with LMWH at 10 and 50 U/mL. Chemotaxis of neutrophils in resp onse to 100 mu M PAF was significantly decreased to 70.02 +/- 6.4% (n = 8) of the control response by pretreatment of cells with 50 U/mL LMW H. We conclude that LMWH has anti-inflammatory effects on porcine neut rophils, which includes attenuation of cell activation and chemotaxis in response to the lipid-derived inflammatory mediator, PAF.