Summary. Monocyte kinetics were studied in eight normal subjects and 27 patients suffering from various diseases: acute, subacute and chronic infections, malignant tumours, Boeck's sarcoid, neutropenia, and diseases associated with chronic exanthemata or splenomegaly. Autotransfusion of blood cells labelled with 3H‐diisopropylfluorophosphate in vitro was carried out and the fate of these cells in vivo was followed by autoradiographs of leucocyte concentrates prepared from venous samples. Within a few minutes the transfused monocytes equilibrated with the total blood monocyte pool (TBMP). As TBMP proved to be larger than the circulating monocyte pool (CMP), the existence of a marginal monocyte pool (MMP) was postulated. In normal subjects the CMP:MMP ratio averaged 1:3.5. Moderate deviations occurred in disease states. Monocytes left the vascular system at an exponential rate, the mean normal T4 being 8.4 hr. Slight prolongation of T4 was observed in some patients with monocytosis, the maximal values reaching 15 hr. Shortened T4 was found in one patient with acute infection (4.0 hr) and in another with gross splenomegaly (3.5 hr). The monocyte turnover rate (MTR) in normal subjects averaged 6 × 108 monocytes/hr or 7 × 106 monocytes/hr/kg. Highly significant positive correlations were evaluated between the blood monocyte count and TBMP or MTR respectively.
Information on the structure of human monocytopoiesis was derived from the chronologies of labeled monocytes entering the blood following injection of 3H-thymidine (3H-TDR) and 3H-diisopropylfluorophosphate (3H-DFP). It was found that monocytes are released into the blood directly from a proliferating precursor pool. The marrow cell egress was almost completely restricted to G1-phase monocytes. The egress rate increased with maturation time of promonocytes. The majority of the cells was released at maturation times between 50 and 60 hr. Under normal conditions promonocytes underwent a mean of two catenated cell cycles. The cell cycle time averaged 29 hr and DNA-synthesis time 10 hr. Direct investigations of the promonocytes demonstrated that the medullary promonocyte pool averages 6 x 108 cells/kg body weight in healthy adults. This pool produces a mean of 7 x 106 cells/kg-hr. Proliferation capacity of promonocytes is only partially utilized in normal monocytopoiesis. Induction of acute inflammatory reactions gave rise to an immediate enhancement of promonocyte proliferation activity, thus affording short-term adaptation of monocyte production to monocyte demand. Increase in monocyte production was associated with a shift of marrow release in favor of immature cells.
Monocytopoiesis and blood monocytes were investigated in nine patients with active tuberculosis and in six patients with active sarcoidosis in order to obtain information on monocyte consumption in these two types of granuloma. All patients with tuberculosis demonstrated a marked increase in proliferation activity of monocytopoiesis and premature monocyte marrow release. These changes indicate a high monocyte consumption which probably is caused by a high macrophage death rate due to the high macrophage-toxicity of tubercle bacilli. Thus, tuberculous lesions are an example of a "high turnover granuloma". In sarcoidosis monocytopoiesis showed no significant deviations from the normal. This indicates a low macrophage turnover or "low turnover granuloma". Thus, any hypothetical agent assumed to be involved in the pathogenesis of sarcoidosis would have to possess low macrophage-toxicity.
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