TY - JOUR
T1 - Sex-dependent effect of aging on calcium signaling and expression of TRPM2 and CRAC channels in human neutrophils
AU - Vázquez-Prieto, María de los Ángeles
AU - Lascurais-Santamaría, Nallely
AU - Fernández-Eufrasio, Nilda Belén
AU - Montiel-Condado, Dvorak
AU - Garibay-Escobar, Adriana
AU - Patiño-López, Genaro
AU - Penner, Reinhold
AU - Sumoza-Toledo, Adriana
N1 - Publisher Copyright:
© 2022 American Society for Histocompatibility and Immunogenetics
PY - 2022/8/1
Y1 - 2022/8/1
N2 - The vulnerability of older adults to bacterial infections has been associated with age-related changes in neutrophils. We analyzed the consequences of aging on calcium (Ca2+) mobilization and TRPM2 and CRAC channels expression in human neutrophils. The percentages of granulocytes, mature neutrophils, and neutrophil precursors were equivalent between young and older adults. However, neutrophil chemotaxis towards IL-8, C5a, or fMLP was lower in older adults of both sexes. Interestingly, a stronger Ca2+ transient followed by an identical Ca2+ influx to IL-8 was observed in older adult females. In addition, the Ca2+ response to LPS was delayed and prolonged in neutrophils of older adult males. There was no significant difference in Ca2+ response to fMLP, C5a, or store-operated Ca2+ entry in the older adults. There were also no differences in the expression of CXCR2, CD88, FPLR1, and TLR4. Interestingly, TRPM2- and ORAI1-mRNA expression was lower in neutrophils of older adults, mainly in females. Both channels were detected intracellularly in the neutrophils. TRPM2 was in late endosomes in young adults and in lysosomes in older adult neutrophils. In summary, defective neutrophil chemotaxis in aging seemed not to stem from alterations in Ca2+ signals; nevertheless, the low TRPM2 and ORAI1 expression may affect other functions.
AB - The vulnerability of older adults to bacterial infections has been associated with age-related changes in neutrophils. We analyzed the consequences of aging on calcium (Ca2+) mobilization and TRPM2 and CRAC channels expression in human neutrophils. The percentages of granulocytes, mature neutrophils, and neutrophil precursors were equivalent between young and older adults. However, neutrophil chemotaxis towards IL-8, C5a, or fMLP was lower in older adults of both sexes. Interestingly, a stronger Ca2+ transient followed by an identical Ca2+ influx to IL-8 was observed in older adult females. In addition, the Ca2+ response to LPS was delayed and prolonged in neutrophils of older adult males. There was no significant difference in Ca2+ response to fMLP, C5a, or store-operated Ca2+ entry in the older adults. There were also no differences in the expression of CXCR2, CD88, FPLR1, and TLR4. Interestingly, TRPM2- and ORAI1-mRNA expression was lower in neutrophils of older adults, mainly in females. Both channels were detected intracellularly in the neutrophils. TRPM2 was in late endosomes in young adults and in lysosomes in older adult neutrophils. In summary, defective neutrophil chemotaxis in aging seemed not to stem from alterations in Ca2+ signals; nevertheless, the low TRPM2 and ORAI1 expression may affect other functions.
KW - Aging
KW - CRAC
KW - Calcium
KW - Neutrophils
KW - TRPM2
UR - http://www.scopus.com/inward/record.url?scp=85131382929&partnerID=8YFLogxK
U2 - 10.1016/j.humimm.2022.05.002
DO - 10.1016/j.humimm.2022.05.002
M3 - Artículo
C2 - 35660323
AN - SCOPUS:85131382929
SN - 0198-8859
VL - 83
SP - 645
EP - 655
JO - Human Immunology
JF - Human Immunology
IS - 8-9
ER -