Leukocytes of the macrophage series are needed for defense reactions
against microbial infections. In addition, they participate in the
development and maintenance of organs and tissues and destroy tumor
Leukocytes which arise during the embryonic period regulate iron metabolism and the growth of the mammary gland in adults.
‘Leukocytes which arise during the embryonic period regulate iron metabolism and the growth of the mammary gland in adults.’
It was previously thought that the tissue-resident macrophages
originate from bone marrow-derived precursors which migrate via the
blood into different organs. However, new research has uncovered that a
significant proportion of macrophages are distributed to the tissues
already before the onset of bone marrow function. These long-lived
embryo-derived macrophages maintain themselves in the adult tissues
through stem cell-like renewal.
Finnish researchers at the University of Turku were the first to
identify the molecular mechanism which controls the migration of early
While studying other topics, we incidentally noticed that a defect
in a certain blood vessel selective protein causes major alterations in
the macrophage distribution. In the absence of this protein, known as
Plvap, the production of the earliest macrophages in the yolk sac and
the development of macrophages after birth were completely normal. In a
striking contrast, the macrophage production in the fetal liver failed
in the absence of Plvap, states Dr. Pia Rantakari.
She and her collaborators found out that the Plvap protein
immobilized attractant cues which guide the migration of macrophage
precursors from the liver to the blood and thereby regulate their
dissemination to different target organs. According to Dr. Rantakari, the
macrophage precursors are in a sense stuck in the liver without the
It was very exciting to learn that a defect in the generation of
such a small macrophage population has dramatic consequences even in
adults. The lack of these macrophages causes an aberrant accumulation of
iron which is continuously released from old red blood cells. Moreover,
the absence of the Plvap protein prevents the maturation of the mammary
gland at puberty almost entirely. These data indicate that it is
precisely these macrophages which are required for the development of
the milk-producing ductal system in the mammary glands, says Dr.
Dr. Rantakari and her collaborators are now busy studying what other
physiological functions are dependent on fetal liver-derived
macrophages. Since macrophage targeting therapies are developed very
actively worldwide, it is also essential to analyze how this particular
macrophage subset is involved in the defense reactions against bacteria
and tumor cells.