Induction of lactoferrin and IL-8 re lease from human neutrophils by tryptic enzymes via proteinase activated receptor-2

Tryptic enzymes such as tryptase, trypsin and thrombin are reportedly able to alter neutrophil behavior. However, little is known of the influence of these proteinases on lactoferrin or IL-8 release from neutrophils. In the present study, we investigated the effects of tryptase, trypsin, thrombin and elastase, and agonist peptides of PAR-1 SFLLR-NH2 and PAR-2 SLIGKV-NH2 and tc-LIGRLO-NH2 on lactoferrin and IL-8 release from highly purified human neutrophils. Flow cytometry shows CD16(+) neutrophils express PARA and PAR-2, but not PAR-3 and PAR-4 proteins. RT-PCR analysis reveals that neutrophils express only PAR-2 genes. Tryptase and trypsin, but not thrombin and elastase, induced significant lactoferrin and IL-8 secretion from neutrophils. SLIGKV-NH2 and tc-LIGRLO-NH2, but not SFLLR-NH2, also stimulated lactoferrin and IL-8 secretion from neutrophils. In conclusion, only a proportion of neutrophils express PARA and/or PAR-2. Tryptase and trypsin-induced lactoferrin and IL-8 secretion from neutrophils most likely occur through activation of PAR-2. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.