Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1-induced PMN functions.
Triggering receptor expressed on myeloid cell-1 (TREM-1) is a recently described receptor that has many effects on polymorphonuclear neutrophil (PMN), as the engagement of this receptor on PMN can induce phagocytosis, respiratory burst and degranulation. We studied the effects of aging on TREM-1 engagement in human PMN. PMN from elderly were found to have impaired response following TREM-1 engagement. Notably they were not able to modulate the TREM-1-induced respiratory burst as PMN from young did. TREM-1 engagement could not reverse PMN survival following incubation with LPS or GM-CSF in the elderly whereas it did in the young. The phosphorylation of TREM-1 signal transduction molecules was altered with aging. Finally, TREM-1 engagement could not drive the recruitment of TREM-1 in the lipid-rafts of the elderly explaining in part the altered response. The observed alterations in TREM-1 response are possibly an important contributing factor in the higher incidence of sepsis-related deaths in the elderly population.
Fortin
Carl F
CF
Immunology Graduate Program, Clinical Research Center, University of Sherbrooke, 3001, 12eme Avenue Nord, Sherbrooke, Que., Canada J1H 5N4.
Lesur
Olivier
O
Fulop
Tamas
T
D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology / Q000502:physiology*; D002470:Cell Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D021962:Membrane Microdomains; D009504:Neutrophils / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D011971:Receptors, Immunologic / Q000378:metabolism / Q000502:physiology*; D016897:Respiratory Burst; D018805:Sepsis / Q000209:etiology / Q000401:mortality; D015398:Signal Transduction; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor