Cellular and Humoral Components of Monocyte and Neutrophil Chemotaxis in Cord Blood

Pahwa, Savita; Pahwa, Rajendra; Grimes, Elena; Smithwick, Elizabeth M.

doi:10.1203/00006450-197705000-00010

Cited by 87 publications

(37 citation statements)

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“…Neutrophils from neonates showed a decreased deformability (1) and a marked deficiency in movement toward different chemotactic stimuli (2)(3)(4)(5)(6). In addition generation of .…”

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confidence: 99%

Phagocytosis-Associated Functions in Neonatal Monocyte-Derived Macrophages

et al. 1988

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A B S T R A n . Using a Teflon culture system we analyzed different aspects of cell maturation and phagocytic activities in neonatal monocyte-derived macrophages. Morphological and cytochemical characteristics as well as the protein composition of neonatal macrophages were identical with those of adult controls; actin binding protein (265,000 Da), myosin (210,000), a-actinin (102,000) and actin (42,000) could be identified in cells from either source: ~l l phagocytic functions were shown to be perfectly normal in neonatal macrophages when compared with adult cells: random migration, chemotactic response to zymosanactivated serum and formyl-methionyl-leucyl-phenylalanin, ingestion, and killing of Staphylococcus aureus, phagocytosis-associated chemiluminescence, production of oxygen intermediates (superoxide anion, 0;; hydrogenperoxide, H202). Phorbol myristate acetate-stimulated 0;-generation by 1 x lo5 macrophages was 11.8 f 4.7 nmol/h for neonates, and 10.2 f 3.9 for controls; production of H 2 0 2 was 7.6 f 3.5 nmol/h in neonatal macrophages and 6.4 +. In newborns, who suffer an increased susceptibility to serious systemic infections, subnormal phagocyte functions have been described. Neutrophils from neonates showed a decreased deformability (1) and a marked deficiency in movement toward different chemotactic stimuli (2-6). In addition generation of .OH by neonatal neutrophils was shown to be decreased (7). However, neonatal monocytes exhibited basically normal phagocytic functions when compared with adult cells (8). The functions of neonatal macrophages have not been fully explored. Macrophages from newborns synthesize humoral host defense factors such as complement components C2, C4 to a similar extent as phagocytes from adults (9, 10); fibronectin production Received October 12, 1987; accepted April 7, 1988. Correspondence Christian P. Speer, M.D., Universitats-Kinderklinik, RobertKoch-Str. 40, D-3400 Gottingen, Federal Republic of Germany.Supported by Grant Sp 239/2-2 from the Deutsche Forschungsgemeinschaft.2 1 was shown to be decreased in neonatal macrophages (9). Macrophages from newborns who had been activated by interferon-7 effectively killed or inhibited replication of toxoplasma gondii (1 I), presentation of bacterial Ag, and production of interleukin 1 was normal in cord blood monocytes/macrophages (12, 13). However, it has been suggested, that the decreased production of interferon-y by human neonatal cells (13) could be due to a functionally immature macrophage (14). Our study was initiated to examine the principal phagocyte activities of monocyte-derived macrophages in response to inflammation, i.e. chemotaxis, phagocytosis, killing, and generation of oxygen metabolites. Momholonical studies included a detailed analysis of the protein compos~ion of macrophages. MATERIALS AND METHODS Cell separation. Umbilical venous blood was withdrawn fromthe placenta into heparin (1-20 U/ml) immediately after delivery of healthy term newborns who were products of an uncomplicated pregnancy, normal labor, and...

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“…Neutrophils from neonates showed a decreased deformability (1) and a marked deficiency in movement toward different chemotactic stimuli (2)(3)(4)(5)(6). In addition generation of .…”

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confidence: 99%

Phagocytosis-Associated Functions in Neonatal Monocyte-Derived Macrophages

et al. 1988

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“…Previous observations have implicated abnormal membrane activity in neonatal PMNs. In addition to deficient chemotaxis (2,4,8), we have observed decreased deformability of neonatal PMNs (5). Mease et al (3) have demonstrated decreased phytohemagglutinin-induced aggregation of human PMNs.…”

Section: Discussionmentioning

confidence: 96%

“…Combined with decreased movement (2,4,8), decreased deformability ( S ) , and decreased lectin-induced aggregation of these cells (3), the data strongly point to a developmental functional PMN membrane abnormality. Whether this functional deficiency derives from a primary membrane defect or an indirect effect of submembranous elements upon the membrane remains to be determined.…”

Section: Discussionmentioning

confidence: 98%

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Reduced Concanavalin A Capping of Neonatal Polymorphonuclear Leukocytes (PMNS)

et al. 1981

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Summaryalso show defective chemotaxis, thereby suggesting an association --between capping and movement in PMNS.-P~Y~~~P~~~~~~~~~ leukocytes (PMNs) have previPMNs from normal human neonates also show deficient themously been shown be chemotactically deficient' To probe the otaxis (2,4,8). To better characterize the nature of this defect, we mechanism(s) responsible for this deficiency, we have investigated studied capping in neonatal PMNs, both spontaneously and in the phenomenon of concanavalin A-induced capping in neonatal response to with colchicine. PMNs. PMNs horn cord blood of 17 healthy, full-term infants and 17 normal adult volunteers were isolated by standard Ficoll-Hypaque and dextran sedimentation. After incubation with and without colchicine, the cells were reincubated with fluorescein isothiocyanate-Con A, fixed, and prepared in wet mounts. Using a fluorescence microscope, PMNs were identified, and the percentage of the capped cells was counted.Upon treatment with colchicine, adult PMNs showed a significant increase in the percentage of capped cells. By contrast, the cord blood PMNs showed no significant increase in capping after colchicine treatment. The difference between percentage of PMNs showing colchicine-induced capping in adult and cord blood was highly significant ( P < 0.01; Student's t test). SpeculationIncreasing evidence suggests that a primary developmental deficiency of neonatal polymorphonuclear leukocyte movement plays an important role in the compromised inflammatory response characteristic of this period of life. The data presented in this report strengthen the argument that the level a t which the developmental deficiency operates is at the cell membrane. Future studies should be directed towards determining whether this represents a primary membrane abnormality or, rather, reflects a defect of cytoskeletal or other submembranous components. Such knowledge-would hopefully lead to improved therapeutic enhancement of the efficiency of neonatal polymorphonuclear leukocyte movement.Chemotaxis of human polymorphonuclear leukocytes (PMNs) involves interactions between the cell membrane and several cytoplasmic cytoskeletal elements-the microtubules and microfilaments. The precise nature of these relationships, however, is unclear. Among the available in vitro probes for characterizing these interactions is "capping," or the accumulation of ligandreceptor complexes at a localized site (9).In lymphocytes, capping can be induced by incubation with polyvalent ligands such as antibodies.Capping in normal human PMNs can abo be demonstrated after exposure to the lectin, concanavalin A (Con A). In normal PMNs, however, Con A capping is significantly increased by incubation of cells with an agent such as colchine, a microtubule disrupter (6).By contrast, PMNs from patients with Chediak-Higashi syndrome do not require preincubation with colchicine and will significantly cap just upon Con A treatment (6, 7). Such PMNs MATERIALS AND METHODSCord blood from normal human term neonates was obtained imm...

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“…Chemotactic dysfunction of CBG has been clearly defined by many investigators (5,6,7,9,13,18). In CBG, response to varying concentrations of chemotactic factor, however, has not been examined, nor compared to ABG.…”

Section: Discussionmentioning

confidence: 99%