Dense distribution of macrophages in flexor aspects of the hand and foot of mid-term human fetuses

Abstract

In the developing human musculoskeletal system, cell death with macrophage accumulation occurs in the thigh muscle and interdigital area. To comprehensively clarify the distribution of macrophages, we immunohistochemically examined 16 pairs of upper and lower extremities without the hip joint (left and right sides) obtained from 8 human fetuses at approximately 10-15 weeks of gestation. Rather than in muscles, CD68-positive macrophages were densely distributed in loose connective tissues of the flexor aspects of the extremities, especially in the wrist, hand and foot. In contrast, no or fewer macrophages were evident in the shoulder and the extensor aspects of the extremities. The macrophages were not concentrated at the enthesis of the tendon and ligament, but tended to be arranged along other connective tissue fibers. Deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling revealed apoptosis in the hand lumbricalis muscles, but not in the area of macrophage accumulation. Likewise, podoplanin-positive lymphatic vessels were not localized to areas of macrophage accumulation. Re-organization of the connective tissue along and around the flexor tendons of the hand and foot, such as development of the bursa or tendon sheath at 10-15 weeks, might require the phagocytotic function of macrophages, although details of the mechanism remain unknown.

Influence of developing ligaments on the muscles in contact with them: a study of the annular ligament of the radius and the sacrospinous ligament in mid-term human fetuses

“…Moreover, in the ANL and SSL, muscle fibers embedded in the ligaments suggested degeneration, or at least impairment of function. In fact, macrophage accumulation has been reported in the fetal ANL at a similar stage [19]. Thus, at these two sites, ligament growth appears not to be "favorable" for the developing muscles, in contrast to the coordinated development and growth that has been hypothesized (see Introduction).…”

Early embryonic development of long tendons in the human foot

“…The hand also carried the common tendinous plate for superficial and deep flexors, but well developed lubricales muscles seem to later separate each of deep tendons (Cho et al, 2012). The destruction of tendinous connections seems to induce macrophage accumulation in the flexor aspect (Kim et al, 2012). In adult human cadavers, the foot planta contains much frequently and greater types of flexor tendon anomalies than in the hand palmar aspect (Bergman et al, 1988).…”

Cell death in the developing vertebrate limb: A locally regulated mechanism contributing to musculoskeletal tissue morphogenesis and differentiation

“…Although the elimination of the tail musculature during metamorphosis of amphibian anura has long been recognized a characteristic model of developmental cell death, muscle remodeling in developing vertebrate limbs has received little attention. In human fetuses, cell death has been functionally associated with myofiber differentiation and innervation of hand and tight muscles 37,38 . In avian embryos, muscle cell death has been analyzed in detail during the formation of muscle bellies of the foot 39 .…”