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ESTIMATION OF EFFECTIVE EOSINOPOIESIS AND BONE MARROW EOSINOPHIL RESERVE CAPACITY IN NORMAL MAN

ESTIMATION OF EFFECTIVE EOSINOPOIESIS AND BONE MARROW EOSINOPHIL RESERVE CAPACITY IN NORMAL MAN Department of Pathology, University of Kiel, Kiel, Federal Republic of Germany (Received 8 December 1977; revision accepted 6 April 1978) ABSTRACT The eosinophil reserve capacity of the post-mitotic granulocyte compartment in the bone marrow and the effective eosinopoiesis in three haematologically normal men have been quantified by means of kinetic parameters of [3Hlthymidine flashlabelled peripheral blood eosinophils. From (a) the time of the appearance in the blood of labelled eosinophils after the tracer injection, (b) the inflow characteristics of the labelled eosinophils in the blood and (c) the magnitude of the eosinophil granulocyte pool in the venous blood, the effective eosinopoiesis (i.e. the eosinophil turnover) was calculated to range between 0.014 and 0.031 x lo9 cells/kg body weight per day (mean 0.22 x lo9 cell/kg per day). The post-mitotic eosinophil reserve capacity of the bone marrow ranged from 0.09 to 0.20 x lo9 cells/kg body weight (mean 0- 14 x lo9 cells/kg). The large reserve pool and the high turnover rate may contribute to sudden rises of the peripheral blood oesinophil counts in some cases of eosinophilia. The peripheral and intramedullary kinetics of normal neutrophilic granulocytes have variously been investigated (Donohue et al., 1958a,b; Cronkite et al., 1960; Killmann et al., 1964; Athens, 1970; Dancey et al., 1976). Corresponding information about normal human eosinophils is confined to a few studies (Parawaresch, Wale & Arndt, 1976; Walle & Parwaresch, 1978). Because the intravascular half-life of eosinophils is short (ca. 8 hr; Parwaresch et a/., 1976) and blood eosinophil counts rise quickly in atopic reactions, it might be expected that considerable storage pool could exist as the underlying cause of sudden eosinophilia in the absence of increased proliferative activity or prolonged intravascular halflife. As in normal humans no sites of eosinopoiesis have been found other than in the bone marrow, we tried to quantify the expected bone marrow eosinophil reserve capacity and effectiveeosinopoiesis in conditions of a normal haematological status. Correspondence: Professor M. R. Parwaresch, Institut fur Pathologie der Universitat Kiel, Hospitalstrasse 42, D-2300 Kiel, Federal Republic of Germany. 0008-8730/79/0500-0249%02.00 @ 1979 Blackwell Scientific Publications A . J. Walle and M . R.Parwaresch MATERIALS AND METHODS Three male subjects, aged 65, 69 and 71 years, who had survived treatment for cancer of the oesophagus and urinary bladder showed normal haematological parameters. They all gave their informed consent to the study. Each of them received an intravenous injection of 0.1 pCi [3Hlthymidine per g body weight (13HlTdR; Radiochemical Center, Amersham; sp. act. 1.9 Ci/mM). Blood samples from the cubital vein were taken at 6 hr intervals from 12 hr until the 6 days post-injection ( p i ) . Absolute leucocyte and eosinophil counts, and differential leucocyte counts, were performed. Leucocyte concentrates (Desaga & Parwaresch, 1970) were used for smear preparations. These were fixed in a mixture of methanol and formol (9 : l), coated with nuclear emulsion (Kodak NTB-2), exposed for 60 days at 4°C in the dark, developed with Kodak D 19 for 3 min at 17OC and stained in a solution of 0.5% eosin, pH 5.5. The labelling index (LI) of 300 eosinophils of each sample was determined. A background correction was performed as follows: the mean number of background grains in surface areas equal to one granulocyte nucleus averaged 1 = 0.85 (range 0.271.79). Assuming a Poisson distribution, the probability for a granulocyte bearing three or more nuclear grains to be biologically labelled was found to amount to 95.6?6. The time of the first appearance of the bulk of labelled eosinophils, the time of the maximum fraction of labelled cells and the inflow characteristics of these labelled eosinophils were used as parameters for estimating the desired data.* Deriuation of formulae (a) The calculation of the total blood eosinophil pool (TBEP) on the basis of the circulating eosinophil pool (CEP) takes into account that the circulating granulocyte pool (CGP) was found to be 44% of the total blood granulocyte pool (TBGP) (Athens, 1970). This value was adopted for eosinophils because of the basic kinetic similarities between neutrophils and eosinophils (Walle & Parwaresch, 1977). Assuming a blood volume of 8% of the body weight the TBEP per kg bodyweight is calculated as follows: (1) TBEP CEP x 0.182 x lo6 The values listed in Table 2 indicate the number of eosinophils in the blood per kg body weight. (b) The simultaneous inflow rate into the CEP of labelled and unlabelled eosinophils together can be derived from the inflow profile of labelled cells between the very low LI of LIETm,, the maximum LI of LI,,, (see Fig. 3). The LI,,, marks the culmination point of and the inflow phase of labelled cells, while LI,,, marks that of the inflow of labelled and unlabelled cells together. Hence, LIT represents the end-point of the replacement of the intravascular cell population by mixed labelled and unlabelled cell cohorts. The ETL,, is calculated from the small triangle in Fig. 3 by means of the method of similar triangles: * Bone marrow aspiration smears from sternal marrow were performed 1 day before the study and stained with Pappenheim's stain. Eosinopoiesis and bone marrow eosinophil reserve LI,, is extrapolated by prolongation of the vertical line through LI,,, up to the LI of 100% (LIloo). The ratio between LI,,, and LIT - ET,!,,,, represents the inflow characteristic d,,,,, and the numerical values indicate the number of cells entering 1.0 pl of blood of the TBEP during a 1 hr period (see Table 2). This, however, is a rough approximation only (see Discussion section). (c) From the TBEP and,,a ,, the turnover rates (TR) of eosinophils in blood can be calculated: TR = TBEP x d,,,,. (3) The numerical values listed in Table 2 indicate the TR as number of eosinophils per kg body weight per day. (d) The marrow eosinophil reserve capacity (MERP) was calculated as follows: MERP = &,,, x TBEP x LIT. (4) The numerical values listed in Table 2 indicate the magnitude of the MERP in terms of eosinophil count per kg body weight. (e) The relations between the numbers of eosinophils in the bone marrow reserve pool and in the intravascular blood pool (MERP :TBEP) are listed in Table 2. RESULTS The leucocyte and eosinophil counts during the 3 weeks before the study were within the same normal range as during the 6 days of the study (Table 1). Pappenheim-stained smears of bone marrow aspirations before the beginning of the study showed normal erythroid/myeloid ratios, and no eosinophilia or other haematological abnormalities. The values of the total blood eosinophil pool (TBEP) per kg body weight were calculated on the basis of the eosinophil counts in the circulating eosinophil pool (CEP, Table l), as listed in Table 2. To evaluate the autoradiograms, all eosinophils with three or more grains per nucleus were considered biologically labelled. Fig. 1 presents the time-dependent LI course of five selected grain classes. Fig. 2 shows the labelling characteristics of the eosinophils of the three patients in terms of the LI as a function of time (pi.). From these curves, four major data were taken from the subsequent calculations: ET,,,, the beginning of the steep rise of the LI; LIE,,,,, the LI at the time of ET,,,; LIT, the time of the maximum LI, indicating the end of one cell TABLE Measured values of kinetic parameters of normal human eosinophils in blood and bone marrow for 1. the period of 3 weeks before the study and during the experimental period Leucocytes per mm3* Subject A B (x Eosinophils per mm3* (%I CEP (Eosinophils per mm3) ET,,, (hr) LIT (hr) LlETmSx LI,,, (%) 5.5 8.5 9.5 (%I 6.2 & 0.8 5.9 +_ 0.6 5.9 0.7 4.0 0.06 4.0 0.05 2.0 f 0.07 CEP = circulating eosinophil pool; ET,,, = time of steep rise in LI; LIT = time of maximum LI; LIETmaI:LI = at time of ET,,,; L,, = maximum LI. I, * Mean and s.d. of the twice daily examinations. A . J. Walle and M . R.Parwaresch 60r 50 - Time ( h r ) FIG. 1. Eosinophil LI LIS time for all cells with three, six, twelve, twenty and thirty-two grains or more per nucleus (grain numbers in parentheses). -2 4 6 0 2 4 6 0 2 4 6 Time (days) FIG.2. Eosinophil labelling indices of patients A, B and C, plotted against time (p.i.). Cells with three or more grains are recorded. Eosinopoiesis and bone marrow eosinophil reserve TABLE Calculated kinetic parameters of normal human bone eosinophils in blood and bone marrow (see text) 2. TB EP (cells/kg x 10-7 ~ ~ ~ *B, ,E Subject A B C ~~~ (ceIls/pl per hr) TR (cells/kg per day x 0.03 I 0.019 0.014 MERP (cell/kg x BM :B 5.1~1 3.7:1 3.7:1 TBEP = total blood eosinophil pool; TBBP = rate of inflow into blood of labelled and unlabelled cells; TR = turnover rate of blood eosinophils; MERP = marrow eosinophil reserve pool; B M : B = ratio of numbers of eosinophils in bone marrow and blood. 60 - 20 ' ( T,) E; f t 4 t ( T) E, (LIT) Time (davs) Time ldovs) . ,.. FIG.3. Schematic representation of the inflow characteristics into the blood (thick lines) of labelled (ET;,, - LI,,J and labelled and unlabelled cells (ETL,, - LI,oo) derived from the labelling index curve of patient B (thin line). For abbreviations see test. FIG.4. Schematic representation of the inflow characteristics of labelled eosinophils into the blood in three haematologically normal subjects as derived from the LI curves. Note the close similarity Subject A; (0) (A) C. B; among the three. (0) A . J. Walle and M. R. Parwaresch renewal period in the blood; and the LI,,,, the maximum LI. From these terms, the parameters ETL,, and LI,,, as the determinants of the steep ascending slope (Fig. 3) could easily be derived as described. The inclination of this slope roughly represents the averaged inflow rate (JTBEP) eosinophils into the blood. These values, as well as those for the turnover rates of (TR), the magnitudes of the marrow eosinophil reserve pools (MERP) and the ratios of numbers of eosinophils in bone marrow and blood (BM/B), are all shown in Table 2. Fig. 4 demonstrates the close similarity among the three patients in the kinetic parameters of their eosinophils. The triangles are derived from the LI curves of Fig. 2. Assuming physiological steady-state conditions, the effective eosinopoiesis is able to maintain, in cases of blocked proliferation, a normal eosinophil turnover for up to 5 days as indicated by LIT (Table l), which defines the end of the first wave of labelled cells. DISCUSSION The application of the [3HlTdR flash-labelling method to eosinophil precursors, followed by the detection of the labelled cells in the blood in order to draw conclusions about the marrow eosinophil reserve capacity and effective eosinopoiesis, is subject to some reservations, most of which have been investigated experimentally. (a) There must be a 'pipeline' transit of cells through the concatenated bone marrow and blood compartments (Cronkite et al., 1960; Cartwright, Athens & Wintrobe, 1964; Athens, 1970; Walle & Parwaresch, 1978). (b) In physiological conditions there must be a steady-state equilibrium between the bone marrow and the blood compartments (Brecher, Foerster & Cronkite, 1962). (c) The label index maximum (LI,,J should reflect not only the culmination point of the intravascular cell renewal process for labelled cells, but also for the mixed labelled and unlabelled cell population. Hitherto, no measurable influence on cell ageing or cell function has been reported for [3HlTdR at the tracer doses used. (d) The relation between the TBEP and the CEP should be similar to that between the TBGP and the CGP (Cartwright eta!., 1964). TABLE Post-mitotic bone marrow pool sizes and turnover rates of neutrophilic granulocytes from the literature. 3. Figures in parentheses indicate the corresponding numbers of eosinophils calculated as 3% (Wintrobe et al., 1974) of the quoted figures Reference Donohue er 01. (1958b) 8.8(0.264) 6.2(0.186) 1.34(0,042)t Parameter Post-mitotic bone marrow pool cells per kg bodyweight (cells x lo-") Granulocytic turnover rate (cells/kg per day x Craddwk er al. (1960) Killmann er Cartwright Deubelbeiss era/. (1975) al. et 01. ( 1964) Dancey er al. (1976) 5.59(0.167) (1964) 8.34(0.250)* 14-5(0.435) 5.6(0.168) 1 ~ 6 7 ( 0 ~ 0 5 0 ) 2.38(0.071)* 1.63(0,0489) 0-87(0.026)$ I .63(O.O48)$ 0.85(0.025) Computed from Killmann's ( I 964) measurements. t Cited after Dancey er a / . (1976). who derived this value from Donohue's measurements. :Obtained after IIHlTdR Rash-labelling in cico. $ Obtained after I'?PIDF labelling in cifro. Eosinopoiesis and bone marrow eosinophil reserve In spite of the hardly negligible objections to the applied cytokinetic method (Table 2), the results seem quite reasonable as compared to those of ferrokinetic and morphological studies. In general, our values range slightly below those cited in Table 3; if, however, they were corrected for the simultaneous disappearance rate of eosinophils from the blood, calculated as the intravascular half-life time (Parwaresch el al., 1976), they come close to those reported in the literature (Table 3). A great advantage of this method for estimating the marrow eosinophil reserve capacity and the magnitude of effective eosinopoiesis is the fact that our results have been obtained from in vivo experiments, under the conditions of undisturbed steady-state balance. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cell Proliferation Wiley

ESTIMATION OF EFFECTIVE EOSINOPOIESIS AND BONE MARROW EOSINOPHIL RESERVE CAPACITY IN NORMAL MAN

W alle , A. J.; P arwaresch , M. R.
Cell Proliferation , Volume 12 (3) – May 1, 1979
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Publisher
Wiley
Copyright
1979 Blackwell Publishing Ltd
ISSN
0960-7722
eISSN
1365-2184
DOI
10.1111/j.1365-2184.1979.tb00147.x
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Abstract

Department of Pathology, University of Kiel, Kiel, Federal Republic of Germany (Received 8 December 1977; revision accepted 6 April 1978) ABSTRACT The eosinophil reserve capacity of the post-mitotic granulocyte compartment in the bone marrow and the effective eosinopoiesis in three haematologically normal men have been quantified by means of kinetic parameters of [3Hlthymidine flashlabelled peripheral blood eosinophils. From (a) the time of the appearance in the blood of labelled eosinophils after the tracer injection, (b) the inflow characteristics of the labelled eosinophils in the blood and (c) the magnitude of the eosinophil granulocyte pool in the venous blood, the effective eosinopoiesis (i.e. the eosinophil turnover) was calculated to range between 0.014 and 0.031 x lo9 cells/kg body weight per day (mean 0.22 x lo9 cell/kg per day). The post-mitotic eosinophil reserve capacity of the bone marrow ranged from 0.09 to 0.20 x lo9 cells/kg body weight (mean 0- 14 x lo9 cells/kg). The large reserve pool and the high turnover rate may contribute to sudden rises of the peripheral blood oesinophil counts in some cases of eosinophilia. The peripheral and intramedullary kinetics of normal neutrophilic granulocytes have variously been investigated (Donohue et al., 1958a,b; Cronkite et al., 1960; Killmann et al., 1964; Athens, 1970; Dancey et al., 1976). Corresponding information about normal human eosinophils is confined to a few studies (Parawaresch, Wale & Arndt, 1976; Walle & Parwaresch, 1978). Because the intravascular half-life of eosinophils is short (ca. 8 hr; Parwaresch et a/., 1976) and blood eosinophil counts rise quickly in atopic reactions, it might be expected that considerable storage pool could exist as the underlying cause of sudden eosinophilia in the absence of increased proliferative activity or prolonged intravascular halflife. As in normal humans no sites of eosinopoiesis have been found other than in the bone marrow, we tried to quantify the expected bone marrow eosinophil reserve capacity and effectiveeosinopoiesis in conditions of a normal haematological status. Correspondence: Professor M. R. Parwaresch, Institut fur Pathologie der Universitat Kiel, Hospitalstrasse 42, D-2300 Kiel, Federal Republic of Germany. 0008-8730/79/0500-0249%02.00 @ 1979 Blackwell Scientific Publications A . J. Walle and M . R.Parwaresch MATERIALS AND METHODS Three male subjects, aged 65, 69 and 71 years, who had survived treatment for cancer of the oesophagus and urinary bladder showed normal haematological parameters. They all gave their informed consent to the study. Each of them received an intravenous injection of 0.1 pCi [3Hlthymidine per g body weight (13HlTdR; Radiochemical Center, Amersham; sp. act. 1.9 Ci/mM). Blood samples from the cubital vein were taken at 6 hr intervals from 12 hr until the 6 days post-injection ( p i ) . Absolute leucocyte and eosinophil counts, and differential leucocyte counts, were performed. Leucocyte concentrates (Desaga & Parwaresch, 1970) were used for smear preparations. These were fixed in a mixture of methanol and formol (9 : l), coated with nuclear emulsion (Kodak NTB-2), exposed for 60 days at 4°C in the dark, developed with Kodak D 19 for 3 min at 17OC and stained in a solution of 0.5% eosin, pH 5.5. The labelling index (LI) of 300 eosinophils of each sample was determined. A background correction was performed as follows: the mean number of background grains in surface areas equal to one granulocyte nucleus averaged 1 = 0.85 (range 0.271.79). Assuming a Poisson distribution, the probability for a granulocyte bearing three or more nuclear grains to be biologically labelled was found to amount to 95.6?6. The time of the first appearance of the bulk of labelled eosinophils, the time of the maximum fraction of labelled cells and the inflow characteristics of these labelled eosinophils were used as parameters for estimating the desired data.* Deriuation of formulae (a) The calculation of the total blood eosinophil pool (TBEP) on the basis of the circulating eosinophil pool (CEP) takes into account that the circulating granulocyte pool (CGP) was found to be 44% of the total blood granulocyte pool (TBGP) (Athens, 1970). This value was adopted for eosinophils because of the basic kinetic similarities between neutrophils and eosinophils (Walle & Parwaresch, 1977). Assuming a blood volume of 8% of the body weight the TBEP per kg bodyweight is calculated as follows: (1) TBEP CEP x 0.182 x lo6 The values listed in Table 2 indicate the number of eosinophils in the blood per kg body weight. (b) The simultaneous inflow rate into the CEP of labelled and unlabelled eosinophils together can be derived from the inflow profile of labelled cells between the very low LI of LIETm,, the maximum LI of LI,,, (see Fig. 3). The LI,,, marks the culmination point of and the inflow phase of labelled cells, while LI,,, marks that of the inflow of labelled and unlabelled cells together. Hence, LIT represents the end-point of the replacement of the intravascular cell population by mixed labelled and unlabelled cell cohorts. The ETL,, is calculated from the small triangle in Fig. 3 by means of the method of similar triangles: * Bone marrow aspiration smears from sternal marrow were performed 1 day before the study and stained with Pappenheim's stain. Eosinopoiesis and bone marrow eosinophil reserve LI,, is extrapolated by prolongation of the vertical line through LI,,, up to the LI of 100% (LIloo). The ratio between LI,,, and LIT - ET,!,,,, represents the inflow characteristic d,,,,, and the numerical values indicate the number of cells entering 1.0 pl of blood of the TBEP during a 1 hr period (see Table 2). This, however, is a rough approximation only (see Discussion section). (c) From the TBEP and,,a ,, the turnover rates (TR) of eosinophils in blood can be calculated: TR = TBEP x d,,,,. (3) The numerical values listed in Table 2 indicate the TR as number of eosinophils per kg body weight per day. (d) The marrow eosinophil reserve capacity (MERP) was calculated as follows: MERP = &,,, x TBEP x LIT. (4) The numerical values listed in Table 2 indicate the magnitude of the MERP in terms of eosinophil count per kg body weight. (e) The relations between the numbers of eosinophils in the bone marrow reserve pool and in the intravascular blood pool (MERP :TBEP) are listed in Table 2. RESULTS The leucocyte and eosinophil counts during the 3 weeks before the study were within the same normal range as during the 6 days of the study (Table 1). Pappenheim-stained smears of bone marrow aspirations before the beginning of the study showed normal erythroid/myeloid ratios, and no eosinophilia or other haematological abnormalities. The values of the total blood eosinophil pool (TBEP) per kg body weight were calculated on the basis of the eosinophil counts in the circulating eosinophil pool (CEP, Table l), as listed in Table 2. To evaluate the autoradiograms, all eosinophils with three or more grains per nucleus were considered biologically labelled. Fig. 1 presents the time-dependent LI course of five selected grain classes. Fig. 2 shows the labelling characteristics of the eosinophils of the three patients in terms of the LI as a function of time (pi.). From these curves, four major data were taken from the subsequent calculations: ET,,,, the beginning of the steep rise of the LI; LIE,,,,, the LI at the time of ET,,,; LIT, the time of the maximum LI, indicating the end of one cell TABLE Measured values of kinetic parameters of normal human eosinophils in blood and bone marrow for 1. the period of 3 weeks before the study and during the experimental period Leucocytes per mm3* Subject A B (x Eosinophils per mm3* (%I CEP (Eosinophils per mm3) ET,,, (hr) LIT (hr) LlETmSx LI,,, (%) 5.5 8.5 9.5 (%I 6.2 & 0.8 5.9 +_ 0.6 5.9 0.7 4.0 0.06 4.0 0.05 2.0 f 0.07 CEP = circulating eosinophil pool; ET,,, = time of steep rise in LI; LIT = time of maximum LI; LIETmaI:LI = at time of ET,,,; L,, = maximum LI. I, * Mean and s.d. of the twice daily examinations. A . J. Walle and M . R.Parwaresch 60r 50 - Time ( h r ) FIG. 1. Eosinophil LI LIS time for all cells with three, six, twelve, twenty and thirty-two grains or more per nucleus (grain numbers in parentheses). -2 4 6 0 2 4 6 0 2 4 6 Time (days) FIG.2. Eosinophil labelling indices of patients A, B and C, plotted against time (p.i.). Cells with three or more grains are recorded. Eosinopoiesis and bone marrow eosinophil reserve TABLE Calculated kinetic parameters of normal human bone eosinophils in blood and bone marrow (see text) 2. TB EP (cells/kg x 10-7 ~ ~ ~ *B, ,E Subject A B C ~~~ (ceIls/pl per hr) TR (cells/kg per day x 0.03 I 0.019 0.014 MERP (cell/kg x BM :B 5.1~1 3.7:1 3.7:1 TBEP = total blood eosinophil pool; TBBP = rate of inflow into blood of labelled and unlabelled cells; TR = turnover rate of blood eosinophils; MERP = marrow eosinophil reserve pool; B M : B = ratio of numbers of eosinophils in bone marrow and blood. 60 - 20 ' ( T,) E; f t 4 t ( T) E, (LIT) Time (davs) Time ldovs) . ,.. FIG.3. Schematic representation of the inflow characteristics into the blood (thick lines) of labelled (ET;,, - LI,,J and labelled and unlabelled cells (ETL,, - LI,oo) derived from the labelling index curve of patient B (thin line). For abbreviations see test. FIG.4. Schematic representation of the inflow characteristics of labelled eosinophils into the blood in three haematologically normal subjects as derived from the LI curves. Note the close similarity Subject A; (0) (A) C. B; among the three. (0) A . J. Walle and M. R. Parwaresch renewal period in the blood; and the LI,,,, the maximum LI. From these terms, the parameters ETL,, and LI,,, as the determinants of the steep ascending slope (Fig. 3) could easily be derived as described. The inclination of this slope roughly represents the averaged inflow rate (JTBEP) eosinophils into the blood. These values, as well as those for the turnover rates of (TR), the magnitudes of the marrow eosinophil reserve pools (MERP) and the ratios of numbers of eosinophils in bone marrow and blood (BM/B), are all shown in Table 2. Fig. 4 demonstrates the close similarity among the three patients in the kinetic parameters of their eosinophils. The triangles are derived from the LI curves of Fig. 2. Assuming physiological steady-state conditions, the effective eosinopoiesis is able to maintain, in cases of blocked proliferation, a normal eosinophil turnover for up to 5 days as indicated by LIT (Table l), which defines the end of the first wave of labelled cells. DISCUSSION The application of the [3HlTdR flash-labelling method to eosinophil precursors, followed by the detection of the labelled cells in the blood in order to draw conclusions about the marrow eosinophil reserve capacity and effective eosinopoiesis, is subject to some reservations, most of which have been investigated experimentally. (a) There must be a 'pipeline' transit of cells through the concatenated bone marrow and blood compartments (Cronkite et al., 1960; Cartwright, Athens & Wintrobe, 1964; Athens, 1970; Walle & Parwaresch, 1978). (b) In physiological conditions there must be a steady-state equilibrium between the bone marrow and the blood compartments (Brecher, Foerster & Cronkite, 1962). (c) The label index maximum (LI,,J should reflect not only the culmination point of the intravascular cell renewal process for labelled cells, but also for the mixed labelled and unlabelled cell population. Hitherto, no measurable influence on cell ageing or cell function has been reported for [3HlTdR at the tracer doses used. (d) The relation between the TBEP and the CEP should be similar to that between the TBGP and the CGP (Cartwright eta!., 1964). TABLE Post-mitotic bone marrow pool sizes and turnover rates of neutrophilic granulocytes from the literature. 3. Figures in parentheses indicate the corresponding numbers of eosinophils calculated as 3% (Wintrobe et al., 1974) of the quoted figures Reference Donohue er 01. (1958b) 8.8(0.264) 6.2(0.186) 1.34(0,042)t Parameter Post-mitotic bone marrow pool cells per kg bodyweight (cells x lo-") Granulocytic turnover rate (cells/kg per day x Craddwk er al. (1960) Killmann er Cartwright Deubelbeiss era/. (1975) al. et 01. ( 1964) Dancey er al. (1976) 5.59(0.167) (1964) 8.34(0.250)* 14-5(0.435) 5.6(0.168) 1 ~ 6 7 ( 0 ~ 0 5 0 ) 2.38(0.071)* 1.63(0,0489) 0-87(0.026)$ I .63(O.O48)$ 0.85(0.025) Computed from Killmann's ( I 964) measurements. t Cited after Dancey er a / . (1976). who derived this value from Donohue's measurements. :Obtained after IIHlTdR Rash-labelling in cico. $ Obtained after I'?PIDF labelling in cifro. Eosinopoiesis and bone marrow eosinophil reserve In spite of the hardly negligible objections to the applied cytokinetic method (Table 2), the results seem quite reasonable as compared to those of ferrokinetic and morphological studies. In general, our values range slightly below those cited in Table 3; if, however, they were corrected for the simultaneous disappearance rate of eosinophils from the blood, calculated as the intravascular half-life time (Parwaresch el al., 1976), they come close to those reported in the literature (Table 3). A great advantage of this method for estimating the marrow eosinophil reserve capacity and the magnitude of effective eosinopoiesis is the fact that our results have been obtained from in vivo experiments, under the conditions of undisturbed steady-state balance.

Journal

Cell Proliferation – Wiley

Published: May 1, 1979

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