scholarly journals Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 265-269
Author(s):  
RS Oseas ◽  
J Allen ◽  
HH Yang ◽  
RL Baehner ◽  
LA Boxer
Keyword(s):  
Cytochalasin B ◽  
Chemotactic Factor ◽  
Human Lactoferrin ◽  
Endothelial Monolayers ◽  
Aggregation Response ◽  
Specific Granule ◽  
Primary Granule

The reaction of FMLP with granulocytes causes aggregation and degranulation and enhances adherence to endothelium. To evaluate whether prevention of granule extrusion could impair these granulocyte activities, granulocytes were treated with either dexamethasone or hydrocortisone prior to treatment with FMLP. Dexamethasone was added to suspensions of cytochalasin B-treated granulocytes; it markedly impaired the aggregation response of the granulocytes of FMLP. When cytochalasin-B was not used, granulocyte aggregation in response to FMLP or PMA was inhibited by dexamethasone. Although dexamethasone prevented aggregation of cells following stimulation with FMLP or PMA, it failed to prevent the aggregation of granulocytes induced by rabbit lactoferrin. Adherence of granulocytes to human endothelial monolayers was enhanced by FMLP; dexamethasone inhibited the enhancement. However, with the addition of human lactoferrin to the granulocytes exposed to dexamethasone, the cells were able to adhere as well to endothelium as the cells exposed to FMLP but free of dexamethasone. When cytochalasin- B-treated granulocytes were incubated with dexamethasone or hydrocortisone prior to the addition of FMLP, the subsequent release of lactoferrin was substantially blocked, whereas the release of the primary granule products, lysozyme and beta-glucuronidase, was attenuated but not completely blocked. Thus, corticosteroids might block chemotactic-factor-induced granulocyte aggregation by selectively preventing release of specific granule products that contribute to and sustain aggregation.

scholarly journals Mechanism of dexamethasone inhibition of chemotactic factor induced granulocyte aggregation

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 265-269 ◽  
Author(s):  
RS Oseas ◽  
J Allen ◽  
HH Yang ◽  
RL Baehner ◽  
LA Boxer
Keyword(s):  
Cytochalasin B ◽  
Chemotactic Factor ◽  
Human Lactoferrin ◽  
Endothelial Monolayers ◽  
Aggregation Response ◽  
Specific Granule ◽  
Primary Granule

Abstract The reaction of FMLP with granulocytes causes aggregation and degranulation and enhances adherence to endothelium. To evaluate whether prevention of granule extrusion could impair these granulocyte activities, granulocytes were treated with either dexamethasone or hydrocortisone prior to treatment with FMLP. Dexamethasone was added to suspensions of cytochalasin B-treated granulocytes; it markedly impaired the aggregation response of the granulocytes of FMLP. When cytochalasin-B was not used, granulocyte aggregation in response to FMLP or PMA was inhibited by dexamethasone. Although dexamethasone prevented aggregation of cells following stimulation with FMLP or PMA, it failed to prevent the aggregation of granulocytes induced by rabbit lactoferrin. Adherence of granulocytes to human endothelial monolayers was enhanced by FMLP; dexamethasone inhibited the enhancement. However, with the addition of human lactoferrin to the granulocytes exposed to dexamethasone, the cells were able to adhere as well to endothelium as the cells exposed to FMLP but free of dexamethasone. When cytochalasin- B-treated granulocytes were incubated with dexamethasone or hydrocortisone prior to the addition of FMLP, the subsequent release of lactoferrin was substantially blocked, whereas the release of the primary granule products, lysozyme and beta-glucuronidase, was attenuated but not completely blocked. Thus, corticosteroids might block chemotactic-factor-induced granulocyte aggregation by selectively preventing release of specific granule products that contribute to and sustain aggregation.

scholarly journals Effect of the chemotactic factor formyl methionyl-leucyl-phenylalanine and cytochalasin B on the cellular levels of calcium in rabbit neutrophils

FEBS Letters ◽  
1979 ◽  
Vol 100 (1) ◽  
pp. 161-165 ◽  
Author(s):  
R.J. Petroski ◽  
P.H. Naccache ◽  
E.L. Becker ◽  
R.I. Sha'afi
Keyword(s):  
Cytochalasin B ◽  
Chemotactic Factor

scholarly journals Terminally Differentiating Eosinophils Express Neutrophil Primary Granule Proteins as well as Eosinophil-specific Granule Proteins in a Temporal Manner

2017 ◽  
Vol 17 (6) ◽  
pp. 410 ◽  
Author(s):  
Karam Kim ◽  
Sae Mi Hwang ◽  
Sung Min Kim ◽  
Sung Woo Park ◽  
Yunjae Jung ◽  
...  
Keyword(s):  
Specific Granule ◽  
Granule Proteins ◽  
Primary Granule

scholarly journals Concanavalin A induces microtubule assembly and specific granule discharge in human polymorphonuclear leukocytes.

1976 ◽  
Vol 68 (3) ◽  
pp. 781-787 ◽  
Author(s):  
S Hoffstein ◽  
R Soberman ◽  
I Goldstein ◽  
G Weissmann
Keyword(s):  
Concanavalin A ◽  
Binding Sites ◽  
Polymorphonuclear Leukocytes ◽  
Cytochalasin B ◽  
Microtubule Assembly ◽  
Human Neutrophils ◽  
Con A ◽  
Specific Granules ◽  
Specific Granule ◽  
Human Polymorphonuclear Leukocytes

Human neutrophils stimulated by concanavalin A (Con A, 100 microng/ml) contained markedly enhanced numbers of microtubules and discharged peroxidase-negative (specific) but not peroxidase-position (azurophile) granules. Release of lysozyme from specific granules was dose and time dependent, could be inhibitied by alpha-methyl-D-mannoside, and enhanced by cytochalasin B. Many microtubules were associated with internalized plasma membrane bearing Con A binding sites.

scholarly journals Selective neutrophil desensitization to chemotactic factors.

1979 ◽  
Vol 80 (3) ◽  
pp. 564-572 ◽  
Author(s):  
J T O'Flaherty ◽  
D L Kreutzer ◽  
H J Showell ◽  
G Vitkauskas ◽  
E L Becker ◽  
...  
Keyword(s):  
Cellular Response ◽  
Chemotactic Factor ◽  
Polymorphonuclear Neutrophils ◽  
Functional Loss ◽  
Aggregation Response ◽  
Bivalent Cations ◽  
Chemotactic Factors ◽  
Calcium And Magnesium

In the presence of extracellular calcium and magnesium, a series of chemotactic oligopeptides and C5a caused aggregation of human polymorphonuclear neutrophils (PMNs). This cellular response developed rapidly and began to reverse 2 min after exposure to the chemotactin. In the absence of the bivalent cations, none of the chemotactins stimulated the aggregation response. If cells were first exposed to a chemotactin and then treated with calcium and magnesium, aggregation was detected only after addition of the cations, and the magnitude of the response fell sharply as the interval between the addition of chemotactin and addition of cations was lengthened: when this interval exceeded 2 min, aggregation was barely detectable. This loss of reactivity persisted even when cells were re-exposed to fresh chemotactic factor and washed between the first and second exposures. In all instances, however, loss of cellular reactivity was highly selective: cells preincubated with any chemotactic oligopeptide were hyporesponsive to subsequent stimulation with an oligopeptide but remained fully responsive to C5a; cells preincubated with C5A were hyporesponsive to C5a but retained their responsitivity to the oligopeptides. Because this selectivity parallels the known specificities of these chemotactic factors for their receptors in or on the neutrophil, desensitization may reflect functional loss of receptors after stimulation. Alternatively, this selectivity may indicate that morphologically identical neutrophils contain subpopulations of cells with varying reactivities to receptor-bound chemotactic factors. In either event, desensitization may be useful in functionally defining chemotactic factors and their respective receptors. The rapidity of development of desensitization suggests that it may operate to limit or moderate various in vitro and in vivo neutrophil responses to chemotactic factors.

scholarly journals Lactoferrin: a promoter of polymorphonuclear leukocyte adhesiveness

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 939-945 ◽  
Author(s):  
R Oseas ◽  
HH Yang ◽  
RL Baehner ◽  
LA Boxer
Keyword(s):  
Vascular Endothelium ◽  
Polymorphonuclear Leukocytes ◽  
Light Transmission ◽  
Competitive Inhibitor ◽  
Human Lactoferrin ◽  
Myristate Acetate ◽  
Con A ◽  
Specific Granule ◽  
High Concentrations ◽  
Granule Product

Polymorphonuclear leukocytes (PMN) degranulate, adhere to vascular endothelium, or aggregate to each other following exposure of the cells to high concentrations of chemotactic stimuli such as formyl-methionyl- leucyl phenylalanine (FMLP). PMN released the specific granule product lactoferrin more readily in response to chemotactic stimuli, which correlated with promotion of PMN aggregation as measured by light transmission and enhanced PMN adherence. Both concanavalin A (Con-A) and phorbol myristate acetate (PMA), agents that lead to specific granule discharge, induced and sustained human PMN aggregation. Similarly, supernatants, generated from Con-A-treated PMN, aggregated fresh PMN in the presence of alpha-methylmannoside, a competitive inhibitor of the lectin. Anti-human lactoferrin IgG but not normal goat IgG blunted the aggregation elicited by both PMA and FMLP. Both human milk lactoferrin and rabbit PMN lactoferrin aggregated human lactoferrin promoted PMN adherence to endothelial cells. The enhanced PMN stickiness was correlated with the early phase of degranulation. Thus, PMN lactoferrin serves an autoregulatory role to retain PMN at inflammatory sites to amplify the inflammatory response.

scholarly journals Mechanisms of lysosomal enzyme release from human polymorphonuclear leukocytes. Effects of phorbol myristate acetate.

1975 ◽  
Vol 66 (3) ◽  
pp. 647-652 ◽  
Author(s):  
I M Goldstein ◽  
S T Hoffstein ◽  
G Weissmann
Keyword(s):  
Phorbol Myristate Acetate ◽  
Lysosomal Enzyme ◽  
Polymorphonuclear Leukocytes ◽  
Cytochalasin B ◽  
Enzyme Release ◽  
Myristate Acetate ◽  
Azurophil Granule ◽  
Cytoplasmic Microtubules ◽  
Specific Granule ◽  
Human Polymorphonuclear Leukocytes

PMA enhanced release of the azurophil granule enzyme, beta-glucuronidase, as well as lysozyme, from cytochalasin B-treated PMN's exposed to either zymosan particles or C5a. PMA was active at nanomolar concentrations, was not toxic to the cells, and was most effective when present for brief durations (0-1 min) before exposure of the cells to the stimuli. Beta-glucuronidase was not released in significant amounts from PMN's exposed to PMA alone, in the absence of stimuli such as zymosan or C5a. In contrast, only the specific granule enzyme, lysozyme, was released from unstimulated cells. Electron micrographs of cells exposed to PMA revealed an increase in the number of visible cytoplasmic microtubules as compared to control cells. Enhancement of lysosomal enzyme (beta-glucuronidase) release by PMA appears to be independent of effects on release of specific granule enzymes (lysozyme), but rather is likely due to PMA-induced elevations of cellular cGMP.

scholarly journals Abnormal peroxidase-positive granules in “specific granule” deficiency

Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 838-844 ◽  
Author(s):  
RT Parmley ◽  
CS Gilbert ◽  
LA Boxer
Keyword(s):  
Antimicrobial Peptides ◽  
Morphometric Analysis ◽  
Granule Size ◽  
Dense Granules ◽  
Specific Granule ◽  
Primary Granules ◽  
Peroxidase Cytochemistry ◽  
And Control ◽  
Primary Granule ◽  
Control Samples

Abstract “Specific granule” deficiency (SGD) has been previously associated with lactoferrin deficiency. The antimicrobial peptides termed defensins, comprising 30% of normal primary granule proteins, have also been shown to be markedly deficient in SGD. The present study was undertaken to correlate these findings with ultrastructural morphometric analysis and peroxidase cytochemistry. Peroxidase-positive, rim-stained, large, defensin-rich dense granules, previously described as a subpopulation of azurophil or primary granules in normal neutrophils, were markedly decreased in a patient with SGD. Morphometric studies of peroxidase- positive granules indicated an average peroxidase-positive granule area (all profiles) in the patient of 0.019 +/- 0.017 micron 2 (mean +/- SD, n = 941) compared to control values from normal neutrophils of two volunteers of 0.049 +/- 0.033 micron 2 (n = 896) and 0.050 +/- 0.039 micron 2 (n = 873) (P less than 0.001 between patient and control samples). Granule histograms showed a single peak of small peroxidase- positive granules, whereas control samples contained more prominent subpopulations of larger peroxidase-positive granules. The total number of peroxidase-positive granules per 100 micron 2 of cytoplasm in the patient was 255 +/- 124 (mean +/- SD, n = 15 cell profiles), which was similar to control values of 266 +/- 63 and 212 +/- 109. Thus, the defensin deficiency in SGD is associated with a decrease in size rather than number of peroxidase-positive granules; suggesting that defensins contribute to normal peroxidase-positive granule size and that SGD is a more global granule deficiency than originally thought.(ABSTRACT TRUNCATED AT 250 WORDS)

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