Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants

• DOI: 10.1189/jlb.70.6.969
• Publication Date: 2022-09-28T01:25:47Z
• Authors: Barry Weinberger; Debra L Laskin; Thomas M Mariano; Vasanthi R Sunil; Christina J DeCoste; Diane E Heck; Carol R Gardner; Jeffrey D Laskin
• Keywords: Adult; Chemotactic Factors; Neutrophils; Infant, Newborn; Antibodies, Monoclonal; Fetal Blood; 3. Good health; N-Formylmethionine Leucyl-Phenylalanine; Chemotaxis, Leukocyte; 03 medical and health sciences; 0302 clinical medicine; Humans; Calcium; Signal Transduction

Potential mechanisms underlying impaired chemotactic responsiveness of neonatal neutrophils were investigated. Two distinct chemoattractants compared: bacterially derived N-formyl-methionyl-leucyl-phenylalanine (fMLP) and a unique monoclonal antibody, designated DL1.2, which binds to neutrophil antigen with an apparent molecular mass 120 kDa. Chemotaxis toward fMLP, as well was reduced in neonates when compared adult cells. This did not appear be result decreased fMLP receptor or DL1.2 expression by neutrophils. but induced rapid increase intracellular calcium cells, reached maximum within 30 s. The response cells from unresponsive subpopulation identified. NF-kappaB nuclear binding activity the p65 subunit IkappaB-alpha, also significantly In contrast, although activated p42/44 p38 mitogen-activated protein (MAP) kinases neutrophils, no differences observed between adults neonates. blocked similar extent inhibitors phosphatidylinositol 3-kinase, inhibitor NF-kappaB. These findings indicate that is of, at least part, aberrations chemoattractant-induced signaling. However, biochemical pathways mediating this defect related specific chemoattractant.