Abstract
In an attempt to determine the mechanism of the profound defect in chemotaxis observed in the polymorphonuclear leukocytes (PMN) of human neonates, we have examined membrane potential changes and alterations in free intracellular calcium following chemotactic factor stimulation. Following exposure to formyl-methionyl-leucyl-phenylalanine (FMLP), PMN from adult donors (11) showed a marked change in membrane potential (31%) as determined by fluorescence emission using the cyanine dye, 3-3-dipentyloxacarbocyanine [DiOC5(3)]. In marked contrast, FMLP-stimulated PMN from 10 human neonates failed to show any significant change in membrane potential (1-2%). Using the calcium-sensitive probe Quin 2/AM, FMLP induced an increase in fluorescence of up to 51% in adult PMN (10). In contrast, the change in intracellular free calcium induced in neonatal PMN was much less (32%; P less than 0.01). These results suggest that the profound defect in chemotactic responsiveness of PMN from human neonates may result from an inability of these cells to undergo changes in membrane potential following inflammatory mediator stimulation.
MeSH Terms
Adult
Aminoquinolines
Carbocyanines
Cell Membrane/drug effects,metabolism
Chemotaxis, Leukocyte
Fetal Blood/cytology
Fluorescent Dyes
Humans
Infant, Newborn
Membrane Potentials/drug effects
N-Formylmethionine Leucyl-Phenylalanine/pharmacology
Neutrophils/metabolism
Verapamil/pharmacology
Chemicals
Aminoquinolines
Carbocyanines
Fluorescent Dyes
N-Formylmethionine Leucyl-Phenylalanine
3,3'-dipentyl-2,2'-oxacarbocyanine
Quin2-acetoxymethyl ester
Verapamil
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sacchi F
Hill H R
References (18)
18 references, click to expand
-
The effect of Ca2+ and Mg2+ on the chemotactic responsiveness and spontaneous motility of rabbit polymorphonuclear leukocytes.
Z Immunitatsforsch Exp Klin Immunol. 1972 Jun;143(5):466-76
PMID: 4282929
-
Role of Ca2+ and Mg2+ in some human neutrophil functions as indicated by ionophore A23187.
Infect Immun. 1976 Jan;13(1):146-51
PMID: 175014
-
Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes.
Proc Natl Acad Sci U S A. 1977 Mar;74(3):1204-8
PMID: 265563
-
Transport of sodium, potassium, and calcium across rabbit polymorphonuclear leukocyte membranes. Effect of chemotactic factor.
J Cell Biol. 1977 May;73(2):428-44
PMID: 558197
-
Decreased mononuclear and polymorphonuclear chemotaxis in human newborns, infants, and young children.
Pediatrics. 1977 Oct;60(4):467-72
PMID: 905012
-
The effects of Ca2+ antagonists on Ca2+ accumulation by subcellular fractions of rat myometrium.
Can J Physiol Pharmacol. 1977 Oct;55(5):1028-32
PMID: 562703
-
Functional analysis of neutrophil granulocytes from healthy, infected, and stressed neonates.
J Pediatr. 1979 Sep;95(3):454-60
PMID: 381621
-
Phagocyte function in the neonate: selected aspects.
Pediatrics. 1979 Nov;64(5 Pt 2 Suppl):709-12
PMID: 503694
-
Bactericidal and metabolic function of polymorphonuclear leukocytes.
Pediatrics. 1979 Nov;64(5 Pt 2 Suppl):719-21
PMID: 228238
-
Interaction of chemotactic factors with human polymorphonuclear leukocytes: studies using a membrane potential-sensitive cyanine dye.
J Membr Biol. 1980;52(3):257-72
PMID: 6770097
-
Secretagogue modulation of the response of human neutrophils to chemoattractants: studies with a membrane potential sensitive cyanine dye.
Mol Immunol. 1980 Feb;17(2):191-200
PMID: 6771522
-
Abnormal mobility of neonatal polymorphonuclear leukocytes. Relationship to impaired redistribution of surface adhesion sites by chemotactic factor or colchicine.
J Clin Invest. 1981 Oct;68(4):863-74
PMID: 7287906
-
Calcium movement and membrane potential changes in the early phase of neutrophil activation by phorbol myristate acetate: a study with ion-selective electrodes.
J Cell Biol. 1982 Apr;93(1):129-34
PMID: 7068750
-
Different maturation of neutrophil chemotaxis in term and preterm newborn infants.
J Pediatr. 1982 Aug;101(2):273-4
PMID: 7097428
-
Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator.
J Cell Biol. 1982 Aug;94(2):325-34
PMID: 6980885
-
Mechanism of Ca++ antagonist-induced vasodilation. Intracellular actions.
Circ Res. 1983 Feb;52(2):137-42
PMID: 6297828
-
Chemotactic peptide binding by intact neutrophils from human neonates.
Pediatr Res. 1984 Jan;18(1):63-6
PMID: 6322097
-
Stimulus response coupling in the human neutrophil. II. Temporal analysis of changes in cytosolic calcium and calcium efflux.
J Biol Chem. 1984 Apr 10;259(7):4076-82
PMID: 6323455