Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

Skubitz, Keith M.; Craddock, Philip R.; Hammerschmidt, D. E.; August, J. T.

doi:10.1172/jci110228

Cited by 116 publications

(15 citation statements)

References 32 publications

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“…The agreement of percent aggregation by microscopy with STKR or STKS demonstrated that the number of aggregates counted along with the unaggregated cells was negligible. Our results confirmed the inhibitory role of corticosteroids, at high dosage, on PMN aggregation (Skubitz et al 1981). To explain this, an effect that excludes the FAS action on aggregation should be invoked.…”

Section: Discussionsupporting

confidence: 88%

“…Aggregation induced by the former group of stimuli measures the intrinsic aggregation capacity of neutrophils (Wallis et al 1986), whereas PMN aggregation by plasma or serum, both unactivated and activated, also reflects humoral effects on the aggregation (Craddock et al 1977c;Hashimoto & Hurd 1981;Camussi et al 1981;Abramson et al 1983;Ringertz et al 1985;Berliner et al 1987). On the contrary, high-dose corticosteroids inhibit PMN aggregation in vivo and in vitro (Schumer 1976;Hammerschmidt et al 1979;Skubitz et al 1981).…”

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confidence: 99%

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Assessment of neutrophil aggregation by Coulter® STKR and STKS haematological analysers

Lippi¹,

Bellavite

Schinella³

et al. 2008

Clinical &Amp; Laboratory Haematology

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Summary. We have studied an alternative method to aggregometry for the assessment of human polymorphonuclear (PMN) leucocyte aggregation. This simple, rapid and reliable procedure counts unaggregated cells on both Coulter’STKS and STKR haematological analysers by the impedance principle. Aggregation of PMN was induced by 15 min incubation with fresh autologous serum (FAS) after a 10 min phorbol myristate acetate (PMA) activation of neutrophils in small aliquots (0.25 ml) of suspension containing about 4.0 × 109 PMN/l. Differences (x 100) between count of resting and PMA + FAS treated neutrophils/count of resting PMN reflect percent aggregation. By this procedure, PMN aggregation did not occur in autologous plasma from EDTA anticoagulated whole blood; it was partially inhibited by hydrocortisone, whereas inactivated or Zymosan activated sera gave values similar to those from FAS induced aggregation. PMA aggregation was dependent on Ca2++Mg2+ concentration. Intra‐assay analytical variability did not exceed 4% on either instrument. Reference values (n= 20) of percent PMN aggregation were 50.7 ± 4.7 on STKS and 47.1 ± 4.8 on STKR. Most probably, the interindividual variance was due to the physiological variability of Mg2+ and/or Ca2+ concentrations in FAS. Thus, this procedure reflects the true PMN aggregability status in a given subject, and in a given electrolyte environment.

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

Assessment of neutrophil aggregation by Coulter® STKR and STKS haematological analysers

Lippi¹,

Bellavite

Schinella³

et al. 2008

Clinical &Amp; Laboratory Haematology

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“…The negative correlation of granulocyte adherence and PMN number (figure 2) that we observed is similar to the neutrophilia and hypoadherence that occurs after chemotactic factors are experimentally infused in vivo (5,21,30,(34)(35)(36)(37)(38), and tends to support this hypothesis (39). The granulocyte hyporesponsiveness might also be explained by the presence of significant numbers of immature granulocytes with different functional characteristics (21).…”

Section: Discussionsupporting

confidence: 79%

Granulocyte Adherence in Pulmonary and Systemic Arterial Blood Samples from Patients with Adult Respiratory Distress Syndrome^1–⁴

Zimmerman¹,

Renzetti

Hill

1984

Am Rev Respir Dis

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The accumulation of granulocytes in lung capillaries, caused by increased granulocyte adherence in response to circulating inflammatory mediators, is proposed as one mechanism of pulmonary vascular injury in the adult respiratory distress syndrome (ARDS). The adherence characteristics of granulocytes from humans with this syndrome have, however, not been described. We assayed the granulocyte adherence to nylon fiber columns using whole blood samples collected from the pulmonary artery of 14 patients within 24 h of satisfying criteria for ARDS. The mean value was 83% of that of normal subjects, and granulocyte adherence was less than or equal to control in samples from 10 of 14 patients. Eight of 12 plasma samples, including 7 of 10 from patients with decreased or normal whole blood granulocyte adherence, contained an activity that increased the adherence of granulocytes isolated from normal subjects. These data suggest that granulocytes may become desensitized to a circulating adherence-promoting mediator or that granulocytes with different functional characteristics circulate in some patients with ARDS. Granulocyte adherence varied directly with the circulating platelet number, indicating that adherence may be influenced by cell-cell interactions as well as by humoral mediators. The granulocyte adherence was a mean of 75% of control samples in samples from 3 patients with increased lung uptake of indium-labeled leukocytes, suggesting that granulocyte accumulation in the lung can occur in the absence of markedly enhanced adherence of circulating cells. These data also suggest that alterations in lung endothelial cells, or the local elaboration of inflammatory mediators, may be important determinants of granulocyte accumulation in the pulmonary microvasculature in established ARDS.

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“…Thus, the prevention by dexamethasone of the fall in blood pressure in response to LPS is not related to inhibition of the formation cyclooxygenase metabolites. Whether other well documented actions of glucocorticosteroids, such as inhibition of the release of endorphins (Simatov, 1979) or platelet-activating factor (Braquet et al, 1987), and/or inhibition of neutrophil activation (Goldstein et al, 1976;Hammerschmidt et al, 1979;Schubitz et al, 1981) contribute to the observed haemodynamic effects of dexamethasone in endotoxic shock warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide‐mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock

Szabó

Mitchell

Thiemermann

et al. 1993

British J Pharmacology

388

276

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1 The role of an enhanced formation of nitric oxide (NO) and the relative importance of the constitutive and inducible NO synthase (NOS) for the development of immediate (within 60 min) and delayed (at 180 min) vascular hyporeactivity to noradrenaline was investigated in a model of circulatory shock induced by endotoxin (lipopolysaccharide; LPS) in the rat. 2 Male Wistar rats were anaesthetized and instrumented for the measurement of mean arterial blood pressure (MAP) and heart rate. In addition, the calcium-dependent and calcium-independent NOS activity was measured ex vivo by the conversion of [3H]-arginine to [HJ-citrulline in homogenates from several organs obtained from vehicle-and LPS-treated rats. 3 E. coli LPS (10mg kg-', i.v. bolus) caused a rapid (within 5 min) and sustained fall in MAP. At 30 and 60 min after LPS, pressor responses to noradrenaline (0.3, 1 or 3 jig kg-', i.v.) were significantly reduced. The pressor responses were restored by N0-nitro-L-arginine methyl ester (L-NAME, 1 mg kg-', i.v. at 60 min), a potent inhibitor of NO synthesis. In contrast, L-NAME did not potentiate the noradrenaline-induced pressor responses in control animals. 4 Dexamethasone (3 mg kg-', i.v., 60 min prior to LPS), a potent inhibitor of the induction of NOS, did not alter initial MAP or pressor responses to noradrenaline in control rats, but significantly attenuated the LPS-induced fall in MAP at 15 to 60 min after LPS. Dexamethasone did not influence the development of the LPS-induced immediate (within 60 min) hyporeactivity to noradrenaline. However, dexamethasone pretreatment prevented the hypotension and vascular hyporeactivity at 180 min. 5 At 60 min after LPS a moderate increase in the activity of a calcium-independent (inducible) NOS activity was detected in the aorta, but not in any of the other tissues studied. However, at 180 min after LPS, a significant NOS induction was observed in the lung, liver, spleen, mesentery, heart and aorta. This NOS induction was substantially prevented by pretreatment with dexamethasone. 6 These results suggest that the immediate hypotension and vascular hyporeactivity to noradrenaline in endotoxin shock is caused by an enhanced formation of NO due to activation of the constitutive enzyme. The delayed hypotension and vascular hyporeactivity, however, is due to enhanced NO formation by the LPS-induced enzyme.

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Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

Cited by 116 publications

References 32 publications

Assessment of neutrophil aggregation by Coulter® STKR and STKS haematological analysers

Assessment of neutrophil aggregation by Coulter® STKR and STKS haematological analysers

Granulocyte Adherence in Pulmonary and Systemic Arterial Blood Samples from Patients with Adult Respiratory Distress Syndrome^1–⁴

Nitric oxide‐mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock

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Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

Cited by 116 publications

References 32 publications

Assessment of neutrophil aggregation by Coulter® STKR and STKS haematological analysers

Assessment of neutrophil aggregation by Coulter® STKR and STKS haematological analysers

Granulocyte Adherence in Pulmonary and Systemic Arterial Blood Samples from Patients with Adult Respiratory Distress Syndrome1–4

Nitric oxide‐mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock

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Granulocyte Adherence in Pulmonary and Systemic Arterial Blood Samples from Patients with Adult Respiratory Distress Syndrome^1–⁴