Resistin is stored in neutrophil granules being released upon challenge with inflammatory stimuli.
We have recently shown that resistin is a key mediator of arthritis accumulating in the inflamed joints and exerting its pro-inflammatory properties independently of TNFalpha. Here we evaluate neutrophils as a cellular source of resistin. Human neutrophils were subjected to subcellular fractionation where the presence of resistin was assessed using western blot, ELISA, and mass spectrometry. Presence of resistin on the neutrophil surface was visualized by flow cytometry. More than 95% of the neutrophils in circulation and in synovial fluid express resistin on their surface. Stimulation of mature neutrophils with fMLF induced release of resistin into supernatants and increased expression of resistin on the surface. Resistin is mobilized simultaneously with lactoferrin, a protein found in specific granules, and with granule-stored CR3/CD11b. Subcellular fractionation of human neutrophils demonstrated the presence of resistin in azurophilic and in specific granules. Here we show that neutrophils have two pools of resistin, the major one exists in specific granules, and the second on their cell membrane. Release of resistin from the neutrophil granules probably serves the main source of resistin at the site of inflammation.
Boström
Elisabeth A
EA
Department of Rheumatology and Inflammation Research, Göteborg University, Guldhedsgatan 10, 41346 Göteborg, Sweden.
Tarkowski
Andrej
A
Bokarewa
Maria
M
D000328:Adult; D000368:Aged; D001168:Arthritis / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007596:Joints / Q000378:metabolism / Q000473:pathology; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D052243:Resistin / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism* / Q000473:pathology
D039481:CD11b Antigen; C509295:ITGAM protein, human; C499624:RETN protein, human; D052243:Resistin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007781:Lactoferrin