248 
MALARIA 
in detail this origin of macrophages in pare¬ 
tics inoculated with tertian malaria. He 
concludes that the specific endothelium (lit¬ 
toral cells) of the liver, spleen, bone mar¬ 
row and lymph nodes and other macro¬ 
phages of the connective tissues are stimu¬ 
lated to form what he terms “maerophagic 
tissue” in various organs. He believes that 
the blood macrophages arise primarily from 
littoral cells and to a lesser extent from 
ordinary endothelium, especially of the 
brain. The last conclusion regarding the 
capillary endothelium has been questioned 
by Taliaferro and Mulligan (1937). 
As has been demonstrated in malaria of 
monkeys and as probably occurs in malaria 
of man, although it has not been adequately 
studied in the latter, by far the majority 
of new macrophages arise from lympho¬ 
cytes with or without passing through an 
intermediate monocyte stage. This hetero¬ 
plastic cytogenesis of macrophages takes 
place largely in the spleen and results in 
the occurrence, after sufficient malarial 
stimulation, of every conceivable inter¬ 
mediate stage between lymphocyte and 
macrophage or from lymphocyte through 
monocyte to macrophage (PL II; Cf. Fig. 
1 with Fig. 2). These intermediate stages 
occur only rarely under physiological con¬ 
ditions. During malaria they have been 
indiscriminately classified by many investi¬ 
gators as large mononuclears or macro¬ 
phages. In general, the degree of phago¬ 
cytic activity is proportional to the amount 
of cytoplasm of the cell. Under the ex¬ 
treme conditions of exceptionally heavy or 
pernicious infections, small cells, even in¬ 
cluding a few undoubted lymphocytes., 
may be phagocytic (PI. II, Fig. 2). The 
transformation of lymphocytes into macro¬ 
phages in the spleen involves lymphocytes 
chiefly formed in situ, but some may be 
brought to the spleen from other sites by 
the blood. The cytogenesis of macrophages 
also takes place in other parts of the body, 
although to a lesser extent. Thus, hemo- 
cytoblasts, the equivalent of lymphocytes, 
in the bone marrow undoubtedly produce 
some macrophages. 
The occurrence of intermediate stages 
between agranulocytes and macrophages 
does not indicate the direction of the proc¬ 
ess, but the fact that lymphocytes actively 
proliferate by mitosis whereas the various 
macrophages do so to a much lesser extent 
indicates that the lymphocyte is actually 
the “stem cell.” Finally, the investiga¬ 
tions of Maximow and others on the devel¬ 
opmental potencies of the lymphocyte and 
the recent investigations on the origin of 
macrophages in malaria and in other infec¬ 
tions (cf. Conway 1939) supply a func¬ 
tional explanation for lymphoid hyperplasia 
and indicate that the lymphocyte is not an 
end cell with completely unknown func¬ 
tions, but that it, together with the partially 
differentiated monocyte, constitutes an 
easily mobilized source of macrophages. 
(3) Hematology. Reviews of the hema¬ 
tology of human malaria may be found in 
Poch (1903), Seyfarth (1926), Schilling 
(1924), Schilling et al. (1924) and Talia¬ 
ferro and Kliiver (1940). In general, 
changes in the peripheral blood show 
a high correlation with those in the organs 
in regard to erythropoiesis, heterophil 
myelopoiesis and monocytopoiesis, but, 
although they indicate the changes, they 
do not quantitatively reflect those in the 
organs in regard to phagocytosis or the 
heteroplastic development of macrophages. 
Special mention should be made of the 
following points which are discussed in 
detail by Taliaferro and Kliiver (1940) : 
Rubitschung (1925), Bunker (1926) and 
others for man and Taliaferro and Kliiver 
for monkeys have found a pronounced 
transient heterophil leucocytosis associated 
with the segmentation of the parasites. 
As heterophils are only rarely phagocytic 
in either the peripheral blood or organs, 
and then generally only to a minor extent 
(Taliaferro and Mulligan 1937), the func¬ 
tional significance of this finding is not 
clear unless they remove the less easily 
identifiable or more easily digested prod¬ 
ucts of segmentation. Furthermore, many 
authors for man and Taliaferro and Kliiver 
