Immunolocalization of phagocytic cells in normal and degenerated intervertebral discs.
METHODS
An immunohistochemical study on human autopsy lumbar intervertebral discs and surgical specimens was conducted.


OBJECTIVE
To investigate the presence of phagocytic cells within herniated and nonherniated disc tissue and its correlation with disc calcification and degeneration.


BACKGROUND
Increasing knowledge is gathered on the molecular mechanisms of extracellular matrix degradation during the process of disc degeneration. However, the data available on the cells involved in this process are sparse.


METHODS
Three different study populations were investigated: 1) 31 midsagittal tissue slices (age range, 0-86 years) encompassing the complete motion segment were decalcified and stained with a monoclonal antibody against the lysosomal CD68 antigen; 2) 12 additional midsagittal (undecalcified) tissue slices from normal fresh cadavers were resin-embedded and used for colocalization of calcifications (Kossa staining) and CD68-positive cells; and 3) in 53 surgical disc specimens from 32 individuals undergoing lumbar surgical interventions, the abundance of CD68-positive cells was correlated with diagnostic groups and magnetic resonance image findings.


RESULTS
In the discs of fetuses, infants, and adolescents, no labeled cells were seen. However, CD68-positive cells were detected in the nucleus pulposus of all individuals with histomorphologic signs of disc degeneration, predominantly in discs adjacent to cleft formations. Morphologically, CD68-positive cells did not differ from nuclear chondrocytes. In the anulus fibrosus, CD68-positive cells were seen less frequently. In the resin-embedded specimens, CD68-positive cells were not associated with tissue calcifications. In most of the surgical specimens, positive cells in cluster-like arrangements were seen frequently, particularly in areas of vascular ingrowth.


CONCLUSIONS
This is the first study describing the abundant presence of CD68-positive cells in human nonherniated disc nucleus pulposus. The findings additionally suggests that these cells are not invaded monocytes or macrophages, but rather, transformed resident cells. It is assumed that these cells are involved in the phagocytosis of extracellular matrix, and that discal cells therefore promote disc degradation, ultimately leading to a loss of biomechanical properties.
Nerlich
Andreas G
AG
Institute of Pathology, Academic Hospital Munich-Bogenhausen, München, Germany. Andreas.Nerlich@lrz. uni-muenchen.de
Weiler
Christoph
C
Zipperer
Jan
J
Narozny
Martin
M
Boos
Norbert
N
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D002114:Calcinosis / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007403:Intervertebral Disc / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D007405:Intervertebral Disc Displacement / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010586:Phagocytes / Q000378:metabolism / Q000473:pathology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule