title: Induction of lactoferrin and IL-8 release from human neutrophils by tryptic enzymes via proteinase activated receptor-2.
abstract: 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-NH(2) and PAR-2 SLIGKV-NH(2) and tc-LIGRLO-NH(2) on lactoferrin and IL-8 release from highly purified human neutrophils. Flow cytometry shows CD16(+) neutrophils express PAR-1 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-NH(2) and tc-LIGRLO-NH(2), but not SFLLR-NH(2), also stimulated lactoferrin and IL-8 secretion from neutrophils. In conclusion, only a proportion of neutrophils express PAR-1 and/or PAR-2. Tryptase and trypsin-induced lactoferrin and IL-8 secretion from neutrophils most likely occur through activation of PAR-2.
authors.affiliation: Allergy and Inflammation Research Institute, the Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, 22 Xin-ling Road, Shantou 515041, Guangdong Province, China.
authors.forename: Haoyang
authors.initials: H
authors.lastname: Wang
authors.forename: Shaoheng
authors.initials: S
authors.lastname: He
mesh_terms: D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000819:agonists / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology*; D053802:Tryptases / Q000494:pharmacology*
chemical_list: D016209:Interleukin-8; D009842:Oligopeptides; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; C113425:cinnamoyl-LIGRLO-amide; C515806:seryl-arginyl-leucyl-leucyl-argininamide; C515807:seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide; D007781:Lactoferrin; D014357:Trypsin; D053802:Tryptases