Total Blood Granulocyte Pool Research Articles

Effects of treatment of rheumatoid arthritis patients with an antibody against tumour necrosis factor α on reticuloendothelial and intrapulmonary granulocyte traffic

The therapeutic effects of a monoclonal antibody against tumour necrosis factor alpha (TNFalpha) were evaluated objectively in 10 patients with rheumatoid arthritis by 111In-labelled granulocyte imaging before and after treatment, and compared with changes in granulocyte kinetics with respect to the liver, spleen and lungs. Anti-TNFalpha resulted in a decrease in the size of the whole-body pool of marginating granulocytes, as reflected by a significant increase in the 30 min intravascular recovery of labelled granulocytes from 40% (S.D. 10) to 47% (S.D. 16) of injected activity (P<0.02). The 111In contents of the spleen, liver and lungs were unchanged, so the origin of the increment in recovery was presumed to be a reduction in granulocyte margination in inflamed synovium, although this was not quantifiable. The sizes of the granulocyte pools in the liver and lungs, expressed as the 111In content of the organ per unit of circulating 111In-labelled cells, were not significantly different after treatment, but the splenic granulocyte pool decreased by 16% (S.D. 19) (P<0.05). Individual changes in the size of the splenic pool showed no significant correlation with corresponding changes in 30 min recovery or with corresponding indices of inflammation (24 h 111In-granulocyte joint activity and C-reactive protein). We conclude that anti-TNFalpha produces an obvious resolution in inflammatory joint activity that is accompanied by an increased circulating component of the total blood granulocyte pool, as a result of decreased margination at sites of inflammation. Anti-TNFalpha may also produce a specific decrease in splenic granulocyte pooling, independent of any anti-inflammatory effects, although a similar decrease in the lungs, which might be anticipated as a result of reduced cytokine-induced granulocyte activation, could not be detected.

Pulmonary granulocyte kinetics in relation to endothelial and granulocyte activation

The aim of the study was to measure the peripheral blood levels of soluble E-selectin in patients with systemic inflammation and compare them with in vivo granulocyte activation, pulmonary intravascular granulocyte pooling, pulmonary extravascular granulocyte migration and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) aerosol clearance, an index of lung injury. The level of soluble E-selectin was measured by capture ELISA. Granulocytes were labelled with 111In and 99mTc for quantification of pulmonary granulocyte kinetics. The pulmonary vascular granulocyte pool (PGP) was expressed as a fraction of the total blood granulocyte pool. Pulmonary granulocyte migration was quantified on 24-h images using the 111In signal. Granulocyte activation was quantified as the percentage of circulating cells showing shape change ('primed'). Lung injury was assessed from the clearance rate of inhaled 99mTc-DTPA aerosol. Eighteen patients with systemic inflammation were studied: five with inflammatory bowel disease, eight with systemic vasculitis, four with graft versus host disease and one with a recent renal transplant. The peripheral blood levels of soluble E-selectin were significantly elevated in patients with systemic inflammation. The level of soluble E-selectin showed a significant association with granulocyte migration (Spearman rank correlation coefficient, Rs=0.53; P<0.05) but not with PGP or with the percentage of cells showing shape change (P>0.05 for both). Granulocyte migration was bimodal: patients were therefore subdivided into 'migrators' and 'non-migrators'. Soluble E-selectin level, 99mTc-DTPA clearance and PGP, but not the percentage of cells showing shape change, were significantly higher in migrators than in non-migrators. We conclude that pulmonary intravascular granulocyte pooling is increased in the presence of increased numbers of circulating primed granulocytes but increased pooling does not by itself promote granulocyte migration into the lung interstitium. Insofar as an elevated level of E-selectin in peripheral blood reflects vascular endothelial activation, the data are consistent with the notion that pulmonary endothelial activation is required, in addition to granulocyte activation and an expanded PGP, for granulocyte migration into lung parenchyma and, therefore, for lung injury to occur.

Relationship between granulocyte activation, pulmonary granulocyte kinetics and alveolar permeability in extrapulmonary inflammatory disease.

1. The aim of the study was to examine the relationship between granulocyte activation, pulmonary intravascular granulocyte transit, pulmonary extravascular granulocyte migration and lung injury in patients with systemic conditions (bone marrow transplant recipients, inflammatory bowel disease and systemic vasculitis) in which abnormalities of pulmonary granulocyte traffic have previously been reported. 2. A double 111In-99mTc granulocyte labelling technique was used for quantification of granulocyte kinetics in 23 patients, of whom five were control patients. The pulmonary vascular granulocyte pool was measured from dynamic data centred on the 99mTc signal and expressed as a percentage of the total blood granulocyte pool. Granulocyte migration was quantified on 24 h images using the 111In signal. Granulocyte activation was measured as the percentage of cells showing a change in shape. The clearance rate of an inhaled aerosol of 99mTc-diethylenetriaminepenta-acetic acid (DTPA) was used as a marker of lung injury. 3. Pulmonary granulocyte pool, migration, activation and aerosol clearance, although highly variable in the patient groups, were, in general, elevated compared with the controls. 4. Granulocyte activation correlated with pulmonary granulocyte pool (Rs = 0.72, n = 22, P < 0.01), while the t1/2 of DTPA clearance correlated with migration (Rs = -0.84, n = 17, P < 0.01). Fifteen patients had an expanded pulmonary granulocyte pool, of whom six with no evidence of migration, had a normal DTPA clearance, while nine, who had an abnormal migration signal, had an accelerated DTPA clearance. The pulmonary granulocyte pool in these nine was significantly higher than in the six without a migration signal. 5. Activation of granulocytes results in delayed transit through the lung vasculature. With increasing margination, granulocytes migrate into the lung interstitium and injure the lung. An increased intravascular pool does not by itself lead to lung injury.

Plasma lactoferrin levels in leukaemias.

A solid-phase, one-step radioimmunoassay was developed for the determination of plasma lactoferrin concentration. The detection limit of the assay is 150 micrograms/l. Leakage of cellular lactoferrin was minimal when EDTA was used as anticoagulant, while results obtained from serum and from heparinized plasma were not reproducible. The plasma lactoferrin concentration of 35 female and 44 male healthy adults was measured in order to determine normal values. The geometric mean of lactoferrin levels in men is about 10% higher than in women: 483 (200-1500) micrograms/l in men and 446 (200-870) micrograms/l in women. Patients with acute and chronic leukaemias were also studied. In 38 patients with chronic myeloid leukaemia plasma lactoferrin levels were increased by three times while the neutrophil count was ten times higher than normal. Normal lactoferrin concentrations were measured in plasma samples from 15 patients with chronic lymphocytic leukaemia in incomplete remission while no detectable lactoferrin was found in samples from those in relapse (10 patients). In the untreated patients or those in relapse (19 cases) of both acute lymphocytic and myeloid leukaemias, plasma lactoferrin concentrations were undetectable while they seemed to return to normal during remission (3 cases). The data obtained indicate that the determination of plasma lactoferrin concentration might play an important role in facilitating the assessment of total blood granulocyte pool (TBGP).

Plasma lactoferrin in patients with neutropenia.

This study examines the role of plasma lactoferrin in the assessment of neutropenia. In particular, we have studied lactoferrin as an inhibitor of granulopoiesis and as an indicator of the size of the total blood granulocyte pool (TBGP). Plasma lactoferrin concentration was determined in a heterogeneous group of 30 patients with neutropenia. Serial plasma lactoferrin levels in a patient with cyclic neutropenia correlated with the cycles of the neutrophil count. Patients with splenomegaly had a grossly elevated lactoferrin:neutrophil ratio. Most chronic idiopathic neutropenia patients had no real clinical problems and a normal plasma lactoferrin level. The results provide further evidence to support the concept that plasma lactoferrin indicates the size of the TBGP and the lactoferrin: neutrophil ratio indicates the degree of granulocyte margination. There was no evidence to suggest that lactoferrin acting as a feedback inhibitor of granulopoiesis caused neutropenia in these patients.

Quantifizierung von Human Lactoferrin als Entzündungsparameter mittels Enzymimmunoassay vom Sandwich-Typ (ELISA)

Human lactoferrin (Lac) is an iron·binding glycoprotein of Mt 76,000 and is found especially in milk: and many other body fluids, such as tcars, saliva. nasal and bronchial secretions, urine, seminal fluid, and in pancreatic flu.id. Altbough ilie biological significance of Lac is still undcr discussion there is cvjdencc for its anribacterial activity in milk and blood. Olhcr biologieal roles of Lac include regulatory funetions during intestinal iron absorption. in myelopoiesis, in neutrophil aggregation and adherence and in inOammation [11. Lac appears lO be synlhesized mainly by polymorphonuelear leukocyles (PMN). 11 15 localized intraccllularly in the seoondary or spccific granulcs of these ceHs [2]. The ce[[ular comcnt of Lac is around 3 5 )1g/1 06 cells. Nonnally Lac occurs in plasma only in trace amounts. Ouring inflammation it is released from PMN with other lysosomal proteins [3, 4]. Measurement of I..ac may be useful because studies suggest that l.ae-<:oncentrations in blood might reflect the activation of the total blood granulocyte pool [5]. Here we describe an enzyme-(jnked immunosorbcnt assay (ELlSA) fo r human laclOferrin.

Quantification of the distribution of the marginating granulocyte pool in man.

The kinetics of autologous granulocytes, separated from whole blood and labelled with 111In-tropolonate with continuous maintenance in plasma, have been studied in man, using a gamma camera and computer, with the aim of quantifying the distribution of the marginating granulocyte pool (MGP). We have used 3 approaches: dynamic gamma camera imaging immediately following i.v. injection of labelled cells, comparison of the activity signal from 111In-granulocytes with that from previously injected 111In-labelled red cells and absolute quantification of 111In present in liver, spleen and blood. Deconvolution analysis of the hepatic and peripheral blood time activity curves indicated that hepatic granulocyte transit time was 2.5 +/- SE 0.14 min. By comparison with 111In red cells, hepatic transit time was calculated to be 7.4 +/- SE 0.82 that of red cells, which, assuming an hepatic red cell content of 6% that of the total red cell mass, is equivalent to a transit time of 1.8 min. By comparison with 111In red cells, lung granulocyte transit time as a factor of red cel transit time was 5.4 +/- SE 0.7 at 5 min and 2.5 +/- SE 0.13 at 40 min after granulocyte injection. Using these kinetic data, in combination with previously published values for splenic granulocyte transit time, it was calculated that, 5 min after injection, the MGP accounted for 54% of the total blood granulocyte pool (TBGP), was 90% filled, and was distributed between spleen (19%), liver (26%), lung (33%) and the remainder of the body (22%). At 40 min, the MGP accounted for 60% of the TBGP, had equilibrated with the circulating granulocyte pool (CGP), and was distributed between the spleen, liver, lung and remainder of the body according to the following respective percentages: 35, 25, 10 and 30. The total granulocyte contents of the spleen and liver calculated on the basis of the kinetic data were 21% and 22% respectively and in broad agreement with the values, 34 and 23% respectively, calculated from quantitative scanning. It was concluded that about 70% of the body's MGP was present in the spleen, liver and lung. If the MGP is itself 60% of the TBGP then only about 18% of the TBGP marginates in extra-hepatosplenopulmonary sites.

Immunoradiometric assay of plasma lactoferrin

The concentration of lactoferrin, a non-heme iron binding glycoprotein, was determined in more than 1500 EDTA plasma samples by a 2-site solid phase immunoradiometric assay to assess the significance of lactoferrin in plasma and to investigate applications for this assay. The use of commercially available antibody and antigen and a relatively short assay time make this assay more suitable for use in routine clinical laboratories than previous methods. A normal range of 250-750 micrograms/l was established. There was a correlation between plasma lactoferrin concentration and the circulating blood neutrophil count in most patients except those with splenomegaly, post-splenectomy and undergoing intensive chemotherapy. Patients with gross splenomegaly usually had an increased and post-splenectomy patients a decreased lactoferrin/neutrophil ratio indicating a respective increase and decrease in the marginated pool. In patients with acute leukemia after chemotherapy or transplantation plasma lactoferrin levels increased 1 to 5 d before blood neutrophil counts rose. As plasma lactoferrin seems to be derived from neutrophils, its concentration is probably related to the size of the total blood granulocyte pool. Calculation of the lactoferrin/neutrophil ratio demonstrated variations in the size of the bone marrow reserve and the marginated neutrophil pool.

The effect of lithium upon granulocyte production in vitro and in vivo in the mouse.

Following the institution of lithium therapy in the management of manic states, observers noted that leukocytosis and neutrophilia frequently occurred (Risetto and Gassano, 1952; Mayfield and Brown, 1966; O’Connell, 1970; Murphy and Goodwin, 1971; Shopsin and Friedman, 1971). In 1973, Tisman et al. postulated that the neutrophilia was due to an increase in the total blood granulocyte pool and also demonstrated augmentation of granulocyte proliferation in vitro (Tisman et al., 1973). In 1975, it was demonstrated that lithium enhanced colony stimulating activity (CSA) production in mice (Harker et al., 1975), and humans (Joyce and Chervenick, 1975), suggesting that this CSA alteration had a mechanistic role in vivo. In the present study, we have examined the action of lithium upon murine granulocytopoiesis in vivo and in vitro in order to: 1) further define the action of lithium upon CSA production by lung, adherent peritoneal cells, and marrow; 2) to examine the direct effect of lithium upon the proliferation of colony forming cells (CFC) or their progeny; and 3) to test the hypothesis that lithium stimulation of CSA production is due to modulation of cellular cyclic AMP (cAMP) levels.KeywordsPeritoneal CellNephrogenic Diabetes InsipidusColony Form CellHoward Hughes Medical InstituteColony Stimulate ActivityThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Inhibition of granulocyte adherence by lithium: possible relationship to lithium-induced leukocytosis.

Many patients receiving lithium carbonate therapy for psychiatric disorders develop increased neutrophil counts in their peripheral blood (O’Connell, 1970; Shopsin et al., 1971). The mechanism for this neutrophilia is thought to involve the stimulation of increased neutrophil production by the marrow. Addition of lithium carbonate in therapeutic concentrations to soft agar cultures of bone marrow promotes granulocyte colony growth (Tisman et al., 1973) and this promotion has been shown to result from the production of increased colony-stimulating activity (Harker et al., 1977). A recent study of granulocyte kinetics in patients treated with lithium has shown that they develop an increased total blood granulocyte pool, an increased marginal pool, and accelerated granulocyte production (Rothstein et al., 1978). Thus, the mechanism for lithium-induced neutrophilia appears to be the stimulation of increased marrow production, with a resultant increase in total intravascular neutrophil pool.KeywordsLithium ConcentrationNylon FiberPlasma FactorSerum Lithium ConcentrationIncrease Neutrophil CountThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Kinetics and Regulation of Granulocyte Precursors During a Granulopoietic Stress

Studies were performed in splenectomized dogs to investigate the proliferative kinetics of the committed granulocyte-macrophage stem cells (CFU-c) and to evaluate the role of colony-stimulating factor (CSF) in the regulation of granulocytopoiesis. Eight to ten hours following intraperitoneal infusion of starch-saline, the peritoneal cavity was lavaged to remove leukocytes. Three successive lavages (I, II, and III) were done in each dog. The CFU-c concentration in the marrow cells of 4 dogs and in the blood cells of 2, obtained before, during, and after lavages, was assayed in soft-agar medium. The CSF activity of lavage fluids was measured by their ability to stimulate canine marrow cells to form granulocyte-macrophage colonies in soft-agar medium. Each lavage removed 14.6–17.5 × 10 9 cells (more than 75% segmented forms and less than 20% monocytes), and the neutrophils removed were equivalent to 97%-108% of their total blood granulocyte pool. Lavaging caused rapid entry of neutrophils from the marrow into the blood and increased granulocytopoiesis in the marrow from the time of lavage II, as reflected by an increased percentage of granulocytes in the multiplicative compartment. Decreases occurred in the percentage normoblasts in the marrow commencing from the time of lavage II and in absolute reticulocyte count in blood after completion of the lavages. Marrow CFU-c decreased to a minimum (30%-57% of control value in 3 of 4 studies) at lavage I or II. CFU-c recovery with overshoot occurred in 3 of 4 studies by the time of lavage III or a day later. The pattern of blood CFU-c changes was similar to that of the marrow. CSF in lavages I, II, and III was ~5, 2, and 1.8 times the control level, respectively. These results suggest that during an acute need for granulocytes the marrow CFU-c differentiate under the apparent influence of CSF to form granulocytes, and pluripotent hemopoietic stem cells differentiate along the granulocytic line with a concomitant reduction in the erythrocytic line.

Neutrophil marrow release

Neutrophil marrow egress is governed by several processes. The most important are cell maturation, functional behavior of marrow sinusoids and humoral or neuro-vascular factors. Neutrophil release cannot be observed directly but is reflected in the size, cellular composition and kinetics of the nonproliferating pool of granulocytopoiesis in bone marrow and of blood neutrophil pool. These experimentally determined parameters were used as the basis of a mathematical model study. The model describes two catenated compartments, the nonproliferating pool of granulocytopoiesis in marrow and the total blood granulocyte pool. Cell transit from one pool to the other was assumed to be age-dependent. It was expressed by a positive sloping sigmoidal function that defines the egress potential fo the cells that increases with cell maturation. During maturation granulocytopoietic cells develop intense motility which determines the morphology of the cells on smears. Relationship between cell motility and its morphology was defined by functions determining the age-dependent probabilities of cell fixation as metamyelocytes, band- and segmented forms, respectively. The parameters of this model could be so adjusted that all experimental data were matched within experimental errors. Thus, qualitative and quantitative information on neutrophil marrow egress was obtained for normal and pathological states of granulocytopoiesis.

Plasma Myeloperoxidase and Lactoferrin Measured by Radioimmunoassay: Relations to Neutrophil Kinetics

In 31 patients, covering a wide range of blood neutrophil counts and turnover rates, the plasma concentrations of myeloperoxidase and lactoferrin have been measured with radioimmunoassays and compared to neutrophil kinetic parameters, measured with DF32P-labeled neutrophils. It was found that the plasma concentrations of both proteins correlated significantly with the total number of neutrophils in the blood (TBGP=total blood granulocyte pool) as well as with the neutrophil turnover rate (GTR=granulocyte turnover rate), which is evidence that neutrophilic granulocytes are the main suppliers of myeloperoxidase and lactoferrin to the plasma. In contrast to the previously demonstrated better relationship between the GTR and plasma lysozyme, a protein also originating in neutrophil granules, both myeloperoxidase and lactoferrin correlated better with the TBGP. These differences may reflect differences in the mode of release of intragranular proteins from neutrophils to the plasma. The correlation of the plasma lactoferrin concentration with the TBGP was so good as to suggest its use in the clinical assessment of the TBGP.

Neutrophil and Monocyte Kinetics in a Case of Cyclic Neutropenia

Abstract The kinetics of neutrophilic granulocytes and monocytes were examined simultaneously in a patient suffering from cyclic neutropenia. During the remission phase of the disease the observed kinetic data for both cell types did not deviate significantly from the normal range. At a stage just before the minimal blood granulocyte count was reached, the total blood granulocyte pool was diminished and the granulocyte half disappearance time shortened to 2.3 hr. Moreover, the intravascular granulocyte distribution changed in favor of the marginal granulocyte pool. During the neutropenic phase, the intravascular monocyte pools were Increased and monocyte half-disappearance time was prolonged to 14 hr; the monocyte turnover rate was 2.4-fold higher than during remission.

An Unusual Pattern of Neutrophil Kinetics in Sickle Cell Anemia

Abstract Blood neutrophil kinetics were studied withwith DF32P in patients with sickle cell anemia. Neutrophil concentration in venous blood samples and the size of the circulating granulocyte pool (CGP) were high normal or abnormally high in all patients. The total blood granulocyte pool (TBGP) was not increased to the same degree as the CGP so that in part, the neutrophilia associated with sickle cell anemia represents a shift from marginated to circulating blood compartments. The half disappearance time (T½) of blood neutrophils tended to be short so that with an elevated or high normal TBGP the absolute granulocyte turnover rate (GTR) tended to be increased. The fractional GTR was regularly increased. In most types of neutrophilia the T½ tends to be increased rather than shortened and the fractional GTR may be normal, decreased, or increased. The increased fractional GTR observed in sickle cell anemia suggests that the absolute increase in neutrophil loss from the blood is not merely a function of increased pool size as was suggested previouslyy.

Granulocyte kinetic studies in the elucidation of clinical problems

Study of neutrophil granulocyte kinetics following the reinfusion of autologous DFP³²-labelled granulocytes in man allows one to interpret the dynamic abnormalities of granulopoiesis in a wide variety of clinical disorders. The size of the total blood granulocyte pool (TBGP) can be calculated from the number of labelled granulocytes infused and the number found initially in the circulation, using isotope dilution principles. The TBGP is always greater than the circulating granulocyte pool (CGP), due to the presence of granulocytes marginated on the walls of vessels (the margined granulocyte pool, MGP). Granulocytes disappear from the blood in s random fashion, which can be characterized by the half disappearance time (T½) of labelled granulocytes in the blood. The granulocyte turnover rate (GTR) can be derived from the TBGP and the T½. In a steady-state situation the GTR is equal to the rate at which granulocytes are produced by the marrow. The authors used these techniques to study two groups of patients: (a) those with lymphoma, and (b) those with neutropenia due to non-malignant disease. Six of the 8 patients with lymphoma had splenamegaly at the time of study, and 4 of thesr were neutropenic. Five of the 7 other patients with neutropenia also had splenomegaly (three Felty's syndrome, one DLE, one portal hypertension). The majority of patients with splenomegaly had an increased MGP : CGP ratio, but none showed a significant shortening of granulocyte survival. In most cases, granulocytes were being produced at a normal or greater than normal rate. Two patients with splenomegaly (one with lymphoma, one with Felty's syndrome) underwent splenectomy, with an increase in circulating granulocytes in each case. Results in 2 patients with lymphoma without splenomegaly were essentially normal, while 2 patients with neutropenia without splenomegaly showed a normal granulocyte survival, a decrease in granulocyte production and an increase in the MGP CGP ratio.

Serum lysozyme and vitamin B 12 binding capacity in myeloproliferative disorders.

Summary Estimations of serum lysozyme (muramidase), total B12 binding capacity (TB12BC) and folate were performed in 122 patients: 69 with myeloproliferative disorders (39, polycythaemia rubra vera (PRV); 10, chronic granulocytic leukaemia, Ph1‐chromosome positive (CGL); 20, myelosclerosis) and 53 with other disease which affect leucocyte production or turnover (17, monocytic leukaemias; 20, megaloblastic anaemia; 15, neutropenia; and a single case of red cell aplasia progressing to a myeloproliferative disorder).The highest serum lysozyme levels were found in monocytic leukaemia. Serum lysozyme concentrations were also elevated in myelosclerosis and to a lesser extent in CGL and in PRV. High levels in PRV occurred in patients developing myelosclerosis or with active disease, resistant to treatment. Significantly higher concentrations of lysozyme were present in patients with myelosclerosis following PRV than in patients with the primary form of the disease. Patients with myeloproliferative diseases and high lysozyme concentrations tended to have low serum folate levels.Slightly raised levels were found in about 50% of patients with megaloblastic anaemia. Moderately high serum lysozyme concentrations also occurred in patients with neutropenia and hypercellular bone marrows but not in those with hypocellular marrows.TB12BC concentrationswere increased in the myeloproliferative disorders, especially in CGL and to a lesser extent in myelosclerosis and least of all in PRV. The results suggest that serum lysozyme reflects granulocyte turnover (except in monocytic leukaemia) while TB12BC (providing liver function is normal) correlates closely with the total blood (and possibly marrow and splenic) granulocyte pool. The ratio between serum lysozyme and TB12BC proved to be a useful index of the balance between granulocyte turnover and total granulocyte pool in individual patients.

Correlation Between Various Blood White Cell Pools and the Serum B12-binding Capacities

Abstract Twenty-four patients with various hematologic and nonhematologic diseases were studied to correlate the various fractions of the serum B12-binding capacity with the blood granulocyte and leukocyte pools and granulocyte turnover rates. The total blood granulocyte pools correlated well with the serum unsaturated B12-binding capacity, especially with the alpha fraction. At least part of the serum B12-binding protein appears to be derived from the neutrophil and from the eosinophil but little or none from the myeloblast. The serum unsaturated B12-binding capacity appears to be a simple index of the total blood granulocyte pool.

Leukokinetic studies. 13. A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis.

The mechanism by which adrenocortical steroids induce granulocytosis in man has been investigated using granulocytes labeled with radioactive diisopropylfluorophosphate. After an intravenous injection of 200 mg of cortisol was given to five normal subjects, the mean value for the total blood granulocyte pool increased from 79 to 138 x 10(7) cells per kg of body weight and reflected an increase in the size of both the circulating granulocyte pool and the marginal granulocyte pool. When granulocytes in the circulation were labeled with diisopropylfluorophosphate and granulocytosis was induced later by the intravenous administration of cortisol, the rate of decline of granulocyte specific activity was increased, indicating that the blood pool was being diluted at an accelerated rate by unlabeled cells entering from the bone marrow. The rate of egress of granulocytes from the blood pool to an inflammatory exudate was studied by the "skin window" technique. After the administration of cortisol, there was a mean reduction in the cellularity of induced inflammatory exudates of 75%. However, this reduction in cellularity varied considerably from subject to subject (45-98%). From these studies we can infer that steroids induce an absolute granulocytosis by decreasing the rate of egress of cells from the total blood granulocyte pool as well as by increasing the influx of cells from the bone marrow. By model simulation studies of the non-steady state induced by cortisol injection, it has been possible to quantitate these rate changes. In the present studies cortisol injection resulted in a mean decrease in blood granulocyte egress of 74% (1-99%) and a mean increase in cell inflow of 450% (300-750%).

The Effect of Etiocholanolone on Granulocyte Kinetics

Abstract The effect of etiocholanolone on granulocyte kinetics in 12 hematologically normal patients has been investigated using the technic of 3H-DFP labeling of autologous blood in vitro. Baseline determinations of the total blood granulocyte pool (TBGP), the circulating pool (CGP), and the marginated pool (MGP) were performed. The values for the total blood granulocyte pools were similar to those previously reported. Following the administration of etiocholanolone, there was a 98 per cent increase in the TBGP, which was considered to be due to mobilization of granulocytes from the bone marrow reserve. There was no change in the ratio of CGP to MGP. These studies suggest that etiocholanolone may be a useful agent for the estimation of bone marrow reserve.