Human mast cells synthesize and release angiogenin, a member of the ribonuclease A (RNase A) superfamily.
ANG is a plasma protein with angiogenic and ribonucleolytic activity implicated in tumor growth, heart failure, wound healing, asthma, and the composition of the adult gut microflora. Human mast cells (HuMC) are similarly associated with modulation of vascular permeability, angiogenic processes, wound healing, and asthma. We hypothesized that HuMC express and secrete ANG in response to divergent stimuli. ANG expression was evaluated in the LAD2 HMC, the HMC-1, and CD34+-derived HuMC, following exposure to live Escherichia coli, TLR ligands, or neuropeptides and following FcepsilonRI aggregation. Expression and production of ANG were determined by microarray analysis, qRT-PCR, confocal microscopy, and ELISA. Microarray analysis showed that ANG is up-regulated by LAD2 cells exposed to live E. coli. qRT-PCR analysis revealed that LAD2, HMC-1, and HuMC constitutively expressed ANG mRNA and that it was up-regulated by exposure to E. coli. Activation of HuMC by FcepsilonRI aggregation resulted in release of small amounts of ANG (<100 pg/mL), whereas compound 48/80, NGF, LPS, PGN, and flagellin activated HuMC to secrete >160 pg/mL ANG. These observations demonstrate that HuMC store and secrete ANG to a variety of stimuli and suggest that MC-derived ANG is available in the subsequent inflammatory response.
Kulka
Marianna
M
National Research Council, 550 University Ave., Charlottetown, PE, Canada. marianna.kulka@nrc.ca
Fukuishi
Nobuyuki
N
Metcalfe
Dean D
DD
D000818:Animals; D001249:Asthma / Q000097:blood / Q000201:enzymology; D002645:Chickens; D004926:Escherichia coli / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology* / Q000382:microbiology; D009369:Neoplasms / Q000097:blood / Q000201:enzymology; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D012259:Ribonuclease, Pancreatic / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
C046366:angiogenin; D012259:Ribonuclease, Pancreatic