Quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory reaction.

Abstract

The present communication concerns a quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory response as compared with the steady-state condition. During an acute inflammation induced by an intraperitoneal injection of NBCS, the peritoneal macrophages increase 2.5 times and there is a concomitant threefold increase of the monocytes in the peripheral blood. This increase of the peritoneal macrophages could be caused by a local proliferation of these cells or by the recruitment of monocytes from the circulation. The results of the in vitro and pulse-labeling studies demonstrate that the mitotic activity of the peritoneal macrophages is not increased during the inflammatory response, which indicates that the increase in the number of these cells is not due to local proliferation. Evidence is also presented that the small proportion (maximally 4%) of peritoneal macrophages that synthesize DNA are very recently arrived from the circulation. In agreement with this is the finding that a small number (less than 3%) of the peripheral blood monocytes are capable of synthesizing DNA. Since proof was obtained that the macrophages in the inflammatory peritoneal exudate originate from peripheral blood monocytes and the number of these cells in the circulation was also augmented, an increased formation of monocytes in the bone marrow was expected. Because increased monocyte production could be brought about by an increased number of promonocytes and/or an acceleration of the mitotic activity of the promonocytes, the various parameters of the cell cycle of these cells were determined. In normal mice the DNA-synthesis time of the promonocytes was 11.8 h, the cell cycle time 16.2 h, and the G(1) + G(2) + M phases 4.4 h. During the first 12 h of the inflammatory response a significantly shorter DNA-synthesis time (7.6 h) and cell cycle time (10.8 h) was found. At 24 h, these values approximated those found in normal mice. Next, both the total production and the rate of production of the monocytes were calculated and compared for both conditions. This computation showed that the total production of labeled monocytes during the first 48 h of an acute inflammation was 64% greater than in normal mice. The rate of production, calculated in two ways (i.e., from the data of the total production and also from the data of the cell cycle time together with the total number of promonocytes) complemented each other very well. During the first 12 h of the inflammatory response the production rate was increased 1.5 times and then leveled off, reaching almost the normal rate after 24 h. Furthermore, the excellent agreement between the results of the two methods of calculation for the normal steady state confirmed once more that the promonocyte is the direct precursor cell of the monocyte, giving rise to the two monocytes after each division. The kinetics of the monocytes in the peripheral blood was also altered during the inflammatory response. During the first 48 h, twice the normal number of labeled monocytes went from the bone marrow to the peripheral blood and twice the normal number also left the circulation. Furthermore, at least 70% of this increased number of labeled monocytes leaving the circulation migrated into the inflammatory exudate of the peritoneal cavity, leading to a roughly 11-fold increase of labeled peritoneal macrophages.