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L A Boxer

Publications and source records attributed to L A Boxer.

At least 19 recordsLinked to original sources
PubMed1992

Correlation of messenger RNA levels with protein defects in specific granule deficiency.

Neutrophil specific granule deficiency (SGD) is a rare congenital disorder of unknown cause associated with an impaired inflammatory response and an absence of neutrophil secondary granules. Reduced levels of several neutrophil proteins have led to the suggestion that the defect may lie at the level of transcription, a hypothesis that is supported by abnormally low levels of lactoferrin message in the bone marrow of two SGD patients. We have examined the level of seven granule protein RNAs in one SGD patient and have compared them with reported protein levels. We have found the RNA levels for all of these genes to be reduced in proportion to the decreased levels of their respective proteins. These data further support the hypothesis that the reduced protein levels reflect a defect in transcriptional control.

Blood Proteins↗
PubMed1992

Purification of PKC-I, an endogenous protein kinase C inhibitor, and types II and III protein kinase C isoenzymes from human neutrophils.

Human neutrophil protein kinase C (PKC) activity is inhibited by an endogenous protein found primarily in the pellet fraction from homogenized specific granules, which was both heat- and proteinase-sensitive [Balazovich, Smolen & Boxer (1986) J. Immunol. 137, 1665-1673]. We now report that two PKC isoenzymes and the endogenous PKC inhibitor, which we named PKC-I, were purified from human neutrophils. A neutrophil soluble fraction that was subjected to DEAE-Sephacel chromatography yielded highly enriched PKC because, by definition, enzymic activity was strictly dependent on Ca2+ and phosphatidylserine. Hydroxyapatite chromatography resolved two peaks of PKC activity. Type II and Type III PKC isoenzymes were each identified on Western blots by using isoenzyme-specific monoclonal antibodies. Unlike rat brain, from which PKC isoenzymes were also purified, Type I PKC was not detected in human neutrophils. Western blots indicated that both Type II and Type III PKC isoenzymes had molecular masses near 80 kDa. In agreement with other reports, PKC was autophosphorylated in vitro. PKC-I, an endogenous neutrophil inhibitor of PKC, was purified to apparent homogeneity by DEAE-Sephacel and S-400 Sephacel chromatography. PKC-I had a molecular mass of 41 kDa. PKC-I inhibited purified PKC activity stimulated by 1,2-diacylglycerols in a concentration-dependent manner, and inhibited PKC-dependent phosphorylation of proteins present in neutrophil cytosol.

Animals↗
PubMed1992

Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with neutropenia.

The results of an open-label, randomized, Phase III trial of r-methionyl human granulocyte-colony-stimulating factor (r-metHuG-CSF) in 41 patients with severe chronic neutropenia (SCN) are reported. Patients with diagnoses of congenital, cyclic, and idiopathic neutropenia, with histories of recurrent infections, were evaluated. The primary objective of the trial was to evaluate the ability of r-metHuG-CSF to increase the ANC to greater than 1500/mm3. A secondary objective was to evaluate variables associated with infection-related morbidity in SCN. r-metHuG-CSF treatment consisted of 1 month of dose titration followed by 4 months of treatment at an optimal dose. Patients were randomized to either immediate treatment with r-metHuG-CSF (Group A) or four months of observation followed by r-metHuG-CSF treatment (Group B). r-metHuG-CSF was administered by daily, subcutaneous injection with initial doses of 3 to 10 micrograms/kg/day. Forty of 41 patients who received r-metHuG-CSF had a complete response (median ANC greater than 1500/mm3 during 4 months of r-metHuG-CSF treatment). All cases of gingivitis and severe mouth ulcers resolved upon treatment with r-metHuG-CSF. Serious infections were also eliminated. Only one patient failed to show clinical improvement in response to r-metHuG-CSF treatment. Adverse reactions during the first 5 months of treatment were mild. Splenomegaly (mild) was noted in some patients. The administration of r-metHuG-CSF in patients with SCN significantly increased the ANC (P less than 0.001) and was accompanied by a marked reduction in infectious complications.

Agranulocytosis↗
PubMed1992

Human neutrophil annexin I promotes granule aggregation and modulates Ca(2+)-dependent membrane fusion.

The mechanism and cofactor requirements of exocytotic membrane fusion in neutrophils are unknown. Cytosolic proteins have been implicated in membrane fusion events. We assessed neutrophil cytosol for the presence of fusogenic proteins using a liposome fusion assay (lipid mixing). A fusogenic 36-kD protein containing amino acid sequence homology with human annexin I was purified from the cytosol of human neutrophils. This protein also shared functional characteristics with annexin I: it associated with and promoted lipid mixing of liposomes in a Ca(2+)-dependent manner at micromolar Ca2+ concentrations. The 36-kD protein required diacylglycerol to promote true fusion (contents mixing) at the same Ca2+ concentrations used for lipid mixing. The 36-kD protein exhibited a biphasic dose-response curve, by both promoting and inhibiting Ca(2+)-dependent lipid-mixing between liposomes and a plasma membrane fraction. The 36-kD protein also promoted Ca(2+)-dependent increases in aggregation of a specific granule fraction, as measured by a turbidity increase. Antiannexin I antibodies depleted the 36-kD protein from the cytosol by greater than 70% and diminished its ability to promote lipid mixing. Antiannexin I antibodies also decreased by greater than 75% the ability of neutrophil cytosol to promote Ca(2+)-dependent aggregation of the specific granules. These data suggest that annexin I may be involved in aggregation and fusion events in neutrophils.

Annexins↗
PubMed1991

Activation of human neutrophils increases thrombospondin receptor expression.

Thrombospondin (TSP), a 450-kDa extracellular matrix protein secreted by platelets may be instrumental in triggering polymorphonuclear leukocyte (PMN) activation and mediating PMN-endothelial cell interactions. TSP alone had no effect on O-2 generation but caused a significant increase in the chemoattractant FMLP-mediated O-2 generation. Purified HBD, but not the 140-kDa COOH-terminal fragment of TSP, retained the priming activity indicating that the priming effect was mediated through the HBD of TSP. The priming of FMLP-mediated O-2 generation by TSP, and our recent studies demonstrating that TSP stimulates PMN adhesion and motility suggested the presence of specific receptors for TSP on PMN. Binding studies on unactivated PMN, using 125I-TSP and competition with excess unlabeled TSP, demonstrated 2.4 x 10(3) binding sites/cell with an apparent Kd of 7 nM. Heparin did not compete for binding as effectively as unlabeled TSP. There were 1.5 x 10(3) heparin-inhibitable binding sites/cell with an apparent Kd of 8 nM that represented approximately 60% of the TSP-specific sites. Therefore, two distinct TSP receptors appeared to exist on unactivated PMN; one interacting with the heparin-binding domain of TSP and one interacting with a different site. Treating PMN with cytochalasin B followed by FMLP caused a 30-fold increase in TSP receptor expression. Binding studies on activated PMNs revealed 7.6 x 10(4) sites/cell; 60% of which were heparin inhibitable. The majority (5.3 x 10(4) sites/cell) of receptors expressed had an affinity of approximately 20 nM. About 50% of these sites were heparin inhibitable. In addition, there were 2.3 x 10(4) higher affinity sites/cell with an apparent Kd of 6 nM. Heparin-inhibitable sites comprised 70% of the higher affinity sites. The existence of a subset of TSP receptors that were heparin-inhibitable on PMN suggests that binding of TSP may trigger functionally independent responses. Increased receptor expression and expression of two high affinity binding sites following PMN activation may modulate PMN-endothelium or PMN-basement membrane interactions localized at the blood vessel wall.

Amino Acid Sequence↗
PubMed1991

Human neutrophil adherence to thrombospondin occurs through a CD11/CD18-independent mechanism.

Thrombospondin (TSP), a 450-kDa trimeric glycoprotein secreted by platelets and endothelial cells at sites of tissue injury or inflammation, may play an important role in polymorphonuclear leukocyte (PMN) adherence to blood vessel walls before diapedesis. We have examined the adherence of PMN to TSP and compared it to adherence to other extracellular matrix proteins. PMN adherence to TSP-coated plastic was complete by 60 min with spreading completed by 2 h. The kinetics of adhesion and spreading on TSP were similar to that of vitronectin (VN), laminin (LN), and fibronectin (FN). Activation of PMN with the calcium ionophore A23187 or the chemotactic peptide FMLP increased PMN adherence to LN and FN, but not to TSP or VN, suggesting that PMN activation may differentially regulate expression of TSP and VN receptors as compared to LN and FN receptors. The specificity of PMN adherence to TSP was confirmed by competition with saturating amounts of TSP and inhibition with anti-TSP antibodies. mAb A6.1, which binds to the protease-resistant core of TSP, was the most effective in blocking PMN adherence to TSP. Using TSP proteolytic fragments, we demonstrated that the primary interaction of PMN with TSP was mediated through the 140-kDa COOH-terminal domain. Inasmuch as the 140-kDa fragment of TSP contains an Arg-Gly-Asp sequence similar to the cell recognition site of FN and VN, we determined whether RGDS peptides would inhibit PMN adhesion. RGDS did not significantly inhibit PMN adhesion to TSP, VN, or LN, but reduced PMN adhesion to FN by 50%. To determine if PMN adhesion to TSP was mediated by a beta 2 integrin receptor such as LFA-1, MO-1, or p150,95, we performed adhesion assays using PMN isolated from patients with leukocyte adhesion deficiency that lack beta 2 receptors. Leukocyte adhesion deficiency PMN exhibited normal adherence to TSP. In contrast, adherence to VN, LN, and FN was reduced by 95%. Therefore, adherence to TSP is probably not mediated by a beta 2 integrin receptor. These data contribute to the accumulating evidence that PMN can interact with extracellular matrix proteins through a CD11/CD18-independent process.

Antigens, CD↗
PubMed1991

Histamine inhibits cell spreading and C3bi receptor clustering and diminishes hydrogen peroxide production by adherent human neutrophils.

Cell adherence plays a central role in many host defense mechanisms. Human peripheral blood neutrophils possess cell surface receptors that contribute to cell adherence or detachment. Receptors specific for the C3bi cleavage fragment of the third component of complement (CR3) promote adhesion, whereas histamine receptors promote detachment. In the present study, we tested the ability of histamine to down-regulate the physiological effects of CR3 receptors. Histamine decreased the binding of 51Cr-labeled neutrophils to complement-coated surfaces (C3-coated surfaces) in a dose-dependent fashion. Scanning electron microscopic and optical microscopic observations of neutrophils on C3-coated surfaces revealed polarized or spherical cell morphologies in the absence or presence of histamine, respectively. Histamine inhibited the ability of CR3 to cluster on plasma membranes of neutrophils adherent to C3-coated surfaces as shown by fluorescence microscopy. In addition, histamine diminished but did not abolish the FMLP-stimulated increase in plasma membrane CR3 expression as measured by fluorometry. Histamine did not inhibit the release of marker proteins from specific or gelatinase containing granules by neutrophils in suspension. Histamine also diminished the FMLP-stimulated production of respiratory burst oxidants from cells in suspension or cells allowed to adhere to fibrinogen substrates. We suggest that histamine may modulate selective changes in neutrophil function by diminishing adherence and preventing changes in cell shape following cell activation.

Cell Adhesion↗
PubMed1991

Clinical and biologic effects of granulocyte colony stimulating factor in the treatment of myelokathexis.

Successful treatment of a patient with myelokathexis, a rare form of chronic neutropenia associated with recurrent infections, is described. Rapid mobilization of bone marrow neutrophils and improved myeloid morphologic features were observed after treatment with human granulocyte colony stimulating factor. Transient thrombocytopenia and bone pain were observed during treatment. Although neutrophil chemotaxis, superoxide production, and FcRIII surface expression were reduced, the patient improved clinically after restoration of a normal neutrophil count.

Antigens, CD↗
PubMed1991

Thrombospondin binds to Staphylococcus aureus and promotes staphylococcal adherence to surfaces.

Bacterial adherence to surfaces is the determining first step in staphylococcal infections. Activated platelets mediate adherence of staphylococci to tissues during inflammation or infection; however, the molecular mechanisms of this interaction are not clearly understood. Thrombospondin, a large multifunctional glycoprotein, is the principal platelet-stored glycoprotein. It is secreted upon platelet activation and either bound to receptors on the platelet surface or released and incorporated into blood clots and extracellular matrices. To characterize thrombospondin binding to staphylococci, we incubated [125I]thrombospondin with Staphylococcus aureus Cowan 1 in the presence of albumin and separated bound and free thrombospondin by centrifugation. We found that binding was (i) specific, since it was up to 76% inhibitable and up to 60% reversible in the presence of a 100-fold excess of unlabeled thrombospondin, (ii) saturable, with an apparent dissociation constant (Kd) of 5.6 x 10(-9) M and a maximal number of 2,600 binding sites per microorganism, and (iii) Ca2+ dependent, since omission of this ion from the medium decreased significantly the binding capacity. The binding reaction was insensitive to previous trypsin treatment of bacteria, but it was strongly inhibited in the presence of heparin. Protein A-negative and -positive strains had similar binding characteristics. To determine the promotion of staphylococcal adherence to surfaces by solid-phase thrombospondin, we incubated 3H-labeled S. aureus Cowan 1 and 26 pathogenic staphylococcal isolates with thrombospondin-coated polymethylmethacrylate disks and found that adherence was significantly promoted as a function of adsorbed thrombospondin. These results indicate a role for thrombospondin as an important mediator of staphylococcal adherence to activated platelets, to blood clots, or to extracellular matrices in pyogenic infections.

Bacterial Adhesion↗
PubMed1991

Severe congenital neutropenia: clinical effects and neutrophil function during treatment with granulocyte colony-stimulating factor.

We studied neutrophil function and clinical responses in seven patients with severe congenital neutropenia (SCN) after they received treatment with recombinant human granulocyte colony stimulating factor (rhG-CSF). Two subpopulations of patients with SCN were defined by their pattern of absolute neutrophil response, superoxide production, and cytochrome b559 levels. One group had an oscillating absolute neutrophil count and reduced ability to produce superoxide and cytochrome b559 (n = 4), and the second group had a relatively constant absolute neutrophil count response with normal superoxide and cytochrome levels (n = 3). Neutrophils from both groups had decreased surface expression of FcRIII and abnormal upregulation of the C3bi receptor (CR3). All patient neutrophils, however, had normal contents of the primary granule constituent, beta-glucuronidase, and the specific granule constituent, vitamin B 12 binding protein. The clinical response to rhG-CSF was evident by marked improvement in the degree of periodontitis and reduction in the number of oral ulcers in both groups of patients. Although neutrophil function is not completely normal in patients with SCN, it is likely that enough redundancy exists in neutrophil bactericidal capacity to promote normal host response to inflammation.

CD18 Antigens↗
PubMed1991

Recombinant human G-CSF and GM-CSF prime human neutrophils for superoxide production through different signal transduction mechanisms.

Recombinant human granulocyte-colony stimulating factor (G-CSF) and recombinant human granulocyte/macrophage-colony stimulating factor (GM-CSF) stimulate neutrophil production from precursors in the marrow and enhance granulocyte functions in vitro. We studied the effects of G-CSF and GM-CSF on neutrophil superoxide production and secretion. G-CSF and GM-CSF alone stimulated neither superoxide production nor secretion, but both agents primed neutrophils for superoxide production stimulated by either N-formylmethionyl-leucyl-phenylalanine (FMLP) or ionomycin. Optimal priming occurred with G-CSF at 5.3 ng/ml for 20 minutes and for GM-CSF at 1 ng/ml for 60 minutes. Priming by GM-CSF was more readily inhibited by the tyrosine kinase inhibitor ST638 but was unaffected by staurosporine. Conversely, G-CSF priming was inhibited by staurosporine but not by ST638. Neither protein kinase C translocation nor increased protein kinase C activity, however, were observed after G-CSF/GM-CSF treatment. Priming by G-CSF and GM-CSF was sensitive to pertussis toxin, suggesting the involvement of guanine nucleotide-binding proteins (G-proteins). Neutrophils from three siblings with cyclic neutropenia were studied to observe the effects of G-CSF treatment on neutrophil function in vivo; sibling 1 and sibling 2 were treated with G-CSF for 6 months, but sibling 3 was not in the treatment group. Compared with neutrophils from normal donors, neutrophils from sibling 1 and sibling 2 were primed in vivo for superoxide release stimulated by either ionomycin or FMLP. Superoxide released by neutrophils from sibling 3 was similar to control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1990

Calcium-dependent fusion of the plasma membrane fraction from human neutrophils with liposomes.

A cell-free assay monitoring lipid mixing was used to investigate the role of Ca2+ in neutrophil membrane-liposome fusion. Micromolar concentrations of Ca2+ were found to directly stimulate fusion of inside-out neutrophil plasma membrane enriched fractions (from neutrophils subjected to nitrogen cavitation) with liposomes (phosphatidylethanolamine:phosphatidic acid, 4:1 molar ratio). In contrast, right-side-out plasma membranes and granule membranes did not fuse with liposomes in the presence of Ca2+. Similar results were obtained with two different lipid mixing assays. Fusion of the neutrophil plasma membrane-enriched fraction with liposomes was dependent upon the concentration of Ca2+, with threshold and 50% maximal rate of fusion occurring at 2 microM and 50 microM, respectively. Furthermore, the fusion was highly specific for Ca2+; other divalent cations such as Ba2+, Mg2+ and Sr2+ promoted fusion only at millimolar concentrations. Red blood cell (RBC) membranes were used in control studies. Ca2(+)-dependent fusion did not occur between right-side-out or inside-out RBC-vesicles and liposomes. However, if the RBC-vesicles were exposed to conditions which depleted spectrin (i.e., low salt), then Ca2(+)-dependent fusion was detected. Other quantitative differences between neutrophil and RBC membranes were found; fusion of liposomes with RBC membranes was most readily achieved with La3+ while neutrophil membrane-liposome fusion was most readily obtained with Ca2+. Furthermore, GTP gamma S was found to enhance Ca2(+)-dependent fusion between liposomes and neutrophil plasma membranes, but not RBC membranes. These studies show that plasma membranes (enriched fractions) from neutrophils are readily capable of fusing with artificial lipid membranes in the presence of micromolar concentrations of Ca2+.

Adult↗
PubMed1990

Exposure of human neutrophils to exogenous nucleotides causes elevation in intracellular calcium, transmembrane calcium fluxes, and an alteration of a cytosolic factor resulting in enhanced superoxide production in response to FMLP and arachidonic acid.

Exposure of human neutrophils to micromolar concentrations of both hydrolyzable and nonhydrolyzable purine nucleotides caused the generation of transient rises in intracellular calcium (Ca2+), Ca2+ fluxes across the membrane, and primed the cells for enhanced production of superoxide (O2-) when subsequently exposed to agonists such as FMLP and arachidonic acid. The neutrophils were most sensitive to adenosine triphosphate (ATP) and ATP-gamma-S, which produced Ca2+ transients and enhanced O2- production at concentrations as low as 1 to 5 mumol/L, with a doubling of O2- generation at 25 to 50 mumol/L. Adenosine diphosphate (ADP), guanosine triphosphate (GTP), and 5'-adenylylimidodiphosphate (AMP-PNP) required approximately 10-fold higher concentrations to cause similar effects. Adenosine did not cause Ca2+ fluxes or a Ca2+ transient and was inhibitory of O2- production. There was a strong correlation between a nucleotide's ability to generate a Ca2+ response and its ability to enhance O2- generation. Nitrogen cavitation and subcellular fractionation of the neutrophils after a brief exposure to ATP, ATP-gamma-S, and AMP-PNP revealed that the enhanced O2- generating capacity was stable and detectable in a cell-free assay system. By combining variously treated cytosolic and membrane fractions, it was found that the enhanced O2- production was attributable to a modification of a component(s) of the cytosol.

Adenosine↗
PubMed1990

Extracellular adenosine nucleotides stimulate protein kinase C activity and human neutrophil activation.

We studied the effect of adenosine nucleotides on several aspects of the functional activation of human peripheral blood polymorphonuclear leukocytes (PMN). Radiolabeled ATP bound to PMN in a manner suggesting the existence of specific binding sites because: 1) binding was reversed (92 +/- 6%) by 100-fold excess concentrations of unlabeled ATP but minimally by either ADP (43 +/- 12%) or GTP (37 +/- 8%); and 2) binding saturation was achieved (i.e., specific binding did not increase) above 250 microM ATP. Binding studies revealed that significant ATP hydrolysis occurred, even at low temperatures and in the presence of phosphatase inhibitors. Adenosine nucleotides activated signal transduction mechanisms in PMN because: 1) 1 to 100 microM ATP and 5'-adenylylimidodiphosphate (AMP-PNP) stimulated increased production of 1,2-diacylglycerols; 2) ATP (0.5 to 500 microM) and ADP (0.1 to 10 mM) induced increased insoluble protein kinase (PKC) activity in a dose-dependent manner when used at concentrations greater than 50 microM; 3) ATP (greater than or equal to 50 microM) induced a shift in the solubility of phorbol receptors from mostly soluble (89% in untreated cells) to mostly insoluble (68%), whereas ADP, GTP, and GDP were effective at higher concentrations; and 4) greater than or equal to 50 microM ATP stimulated increased phosphorylation of endogenous PMN proteins. AMP-PNP induced PKC activity and phosphoprotein changes that were qualitatively similar to those observed when PMN were treated with ATP, suggesting that extracellular ATP hydrolysis is not required for signal transduction to activate PKC. Functionally, ATP stimulated the secretion of specific (but not azurophil) granules because vitamin B12-binding protein and low levels of lysozyme, but not beta-glucuronidase, were released; qualitatively similar results were obtained by using AMP-PNP. These results suggest that certain adenosine nucleotides employed at physiologically relevant concentrations stimulate increased 1,2-diacylglycerol production, PKC activity, granule secretion, and endogenous phosphoprotein formation in a manner that is independent of extracellular ATP hydrolysis.

Adenine Nucleotides↗
PubMed1990

Thrombospondin stimulates motility of human neutrophils.

Polymorphonuclear leukocytes (PMNs) migrate to sites of inflammation or injury in response to chemoattractants released at those sites. The presence of extracellular matrix (ECM) proteins at these sites may influence PMN accumulation at blood vessel walls and enhance their ability to move through tissue. Thrombospondin (TSP), a 450-kD ECM protein whose major proteolytic fragments are a COOH-terminal 140-kD fragment and an NH2-terminal heparin-binding domain (HBD), is secreted by platelets, endothelial cells, and smooth muscle cells. TSP binds specifically to PMN surface receptors and has been shown, in other cell types, to promote directed movement. TSP in solution at low concentrations (30-50 nM) "primed" PMNs for f-Met-Leu-Phe (fMLP)-mediated chemotaxis, increasing the response two- to fourfold. A monoclonal antibody against the HBD of TSP totally abolished this priming effect suggesting that the priming activity resides in the HBD of TSP. Purified HBD retains the priming activity of TSP thereby corroborating the antibody data. TSP alone, in solution at high concentrations (0.5-3.0 microM), stimulated chemotaxis of PMNs and required both the HBD and the 140-kD fragment of TSP. In contrast to TSP in solution, TSP bound to nitrocellulose filters in the range of 20-70 pmol stimulated random locomotion of PMNs. The number of PMNs migrating in response to bound TSP was approximately two orders of magnitude greater than the number of cells that exhibited chemotaxis in response to soluble TSP or fMLP. Monoclonal antibody C6.7, which recognizes an epitope near the carboxyl terminus of TSP, blocked migration stimulated by bound TSP, suggesting that the activity resides in this domain. Using proteolytic fragments, we demonstrated that bound 140-kD fragment, but not HBD, promoted migration of PMNs. Therefore, TSP released at injury sites, alone or in synergy with chemotactic peptides like fMLP, could play a role in directing PMN movement.

Chemotactic Factors↗
PubMed1990

Effect of age on phorbol-ester stimulation of human neutrophils.

When stimulated by phorbol 12-myristate 13-acetate (PMA), superoxide generation in neutrophils from old volunteers was modestly lower than neutrophils from young subjects. PMA receptor number and affinity were normal. Protein kinase C (PKC) translocation to the membrane was normal but its activation was reduced. PMA-induced total endogenous phosphorylation and phosphorylation of individual proteins showed no age-related differences as determined by SDS-PAGE analysis. These minimal alterations in neutrophil function contrast with the much more significant decrements in superoxide generation and calcium homeostasis noted when neutrophils from old volunteers are stimulated by chemotactic peptide formyl-methionyl-leucine-phenylalanine (FMLP) (Lipschitz et al., 1988). It is well recognized that phorbol activates the cell through a mechanism that bypasses the membrane-receptor. Taken together with our observations with FMLP, these results point to a membrane-associated deficiency in the signal transduction pathway, most likely through receptor coupling or alterations in membrane lipids. They also demonstrate that there is not an overall reduction of metabolic responses in neutrophils from the elderly.

Adult↗