Disease relevance of CD68

• Staining for CD68 also revealed that the grafts had undergone reorganization of the tissue, possibly as a result of fibroblast hyperplasia [1].
• Here we demonstrate that the anti-apoptotic protein, Bcl-2, is highly expressed in RA compared with osteoarthritis synovial tissues, particularly in the CD68-negative, fibroblast-like synoviocyte population [2].
• Marked apoptosis of CD68-negative type II pneumocytes (30 to 80%) was detected in four of the seven (57%) cases of acute lung injury [3].
• A substantial increase in MPs was observed in CNS tissue from patients with HIVE, relative to seronegative controls and patients with acquired immune deficiency syndrome but without encephalitis, as determined by CD68 and CD16 immunohistochemistry [4].
• There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects [5].

Psychiatry related information on CD68

• Finally the increased expression of MHC II and CD68 detected in drug abusers with HIVE compared to nondrug abusers with HIVE suggests that the combination of drug abuse and HIV infection has a greater deleterious effect on the brain than either individual insult on its own [6].
• We have, therefore, examined six brains from cases of sporadic CJD by immunohistochemical labelling of grey and white matter microglia from frontal, parietal, temporal, and occipital lobes, striatum, thalamus, cerebellum and brain stem with RCA-1, LCA, CD68, HLA-DR, and HAM56 [7].

High impact information on CD68

• We have identified a novel lysosome-associated membrane glycoprotein localized on chromosome 3q26.3-q27, DC-LAMP, which is homologous to CD68 [8].
• Immunofluorescence analysis revealed a myelomonocytoid immunophenotype (expression of CD13 and CD68, and lack of lymphoid markers) [9].
• Similar relationships were found in human subcutaneous adipose tissue stained for the macrophage antigen CD68 [10].
• Double staining demonstrated that infiltrating cells staining positive for both PD-ECGF and CD68 were more predominant than those staining positive for both PD-ECGF and CD3 [11].
• PDGF beta receptors were expressed by vascular smooth muscle cells and cells in capillary walls; the receptor protein could not be detected in neurofilament containing structures, T lymphocytes, or CD68 expressing macrophages [12].

Chemical compound and disease context of CD68

• Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa [13].
• Because opioid peptides might be of importance in inflammatory skin diseases, for example psoriasis, sections of skin from psoriatic patients were immunohistochemically stained with antisera against methionine and leucine enkephalin, CD68 (KP1, PG-M1), calprotectin (M747), M130 (Ber-MAC3), CD1a and CD3 [14].
• Immunohistochemistry for COX-2 and CD68 (a tissue macrophage marker) was performed on formalin-fixed, paraffin-embedded (n = 52) and frozen, acetone-fixed (n = 6) sections of human sporadic colorectal adenomas [15].
• A series of 20 normal/hyperplastic prostate glands and 60 prostate carcinomas was investigated by immunohistochemistry, using specific antibodies for thymidine phosphorylase (P-GF.44C), tumour-associated macrophages (CD68), endothelium (CD31) and prostate specific antigen (ER-PR8) [16].
• Filed hematoxylin and eosin (H&E)-stained sections from 30 consecutive colorectal adenomas with a stalk (lined by normal colorectal mucosa) were stained with PAS (for mucopolysaccharides), with CD68 (to label macrophages) and with lysozyme (Muramidase) [17].

Biological context of CD68

• This study also suggests that CD68+ cells are instrumental in the chondrolysis process while vascular cells (endothelial and myoid cells) may be the critical microenvironment at the onset of hematopoiesis [18].
• We have isolated cDNA clones encoding CD68 from a U937 cDNA library by transient expression in COS cells and panning with the anti-CD68 monoclonal antibodies (MoAbs) Y2/131, Y1/82A, EBM11, and Ki-M6 [19].
• Both CD68 and peroxisome proliferator-activated receptor-gamma gene expression were increased in the poorly controlled diabetic group (P < 0.05 for each), whose monocytes also displayed increased attachment to endothelial monolayers (P < 0.0005 vs. nondiabetic control subjects) [20].
• RESULTS: mRNA levels of specific macrophage markers (CD68 and CD14) are correlated with adiposity in sc AT and visceral AT (P < 0.05) [21].
• From 11 to 14 weeks of gestation, CD68-positive and CD40-positive cells, like MHC class II--positive cells, were present throughout the lamina propria; few CD3-positive cells (T cells) were observed [22].

Anatomical context of CD68

• Despite expressing antigens in common with blood monocytes, monocyte-derived dendritic cells, and macrophages, NLCs expressed significantly higher levels of CD68 than these other cell types [23].
• CD68 is a 110-Kd transmembrane glycoprotein of unknown function highly expressed by human monocytes and tissue macrophages [19].
• Consistent with the notion that NLCs are present in vivo, CD14+ splenocytes from CLL patients have NLC morphology and express significantly higher levels of CD68 than CD14+ splenocytes from persons without known B-cell malignancy [23].
• CD68 transcripts are constitutively present in the promonocyte cell line U937 and are upregulated by phorbol myristic acid (PMA) [19].
• Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens (Ber-MAC3, MAC387, CD68) and CD8+ T cell subsets (CD29+, CD45RO+ and CD29-, CD45RO-) was performed [24].

Associations of CD68 with chemical compounds

• Dexamethasone increased expression of CD14, CD36, and CD68, molecules characteristic of monocytes/macrophages and induced CD14+CD83- cells, a subset distinct both from immature DC and mature DC [25].
• All cases of MCD showed strong and diffuse positivity for CD68 and tryptase [26].
• Most CD68 positive giant cells also showed tartrate resistant acid phosphatase activity and prominent expression of CD51 [27].
• Specimens were selected from an initial bank from 40 patients on the basis of significant inflammation on hematoxylin and eosin and CD3 and CD68 monoclonal antibody staining (T cells and macrophages, respectively) [28].
• After administration of mifepristone (6-24 h), there was an increase in immunostaining for leukocyte common antigen (CD45), neutrophil elastase, monocytes (CD68), and matrix metalloproteinases (MMP)-1, -8 and -9 [29].

Physical interactions of CD68

• Exogenous JunB restored AP-1 DNA-binding but did not prevent inhibition of macrosialin expression by C/EBPalpha-ER, indicating that JunB is not the only target relevant to inhibition of monopoiesis by C/EBPalpha [30].
• Accumulation of macrophages labeled with monoclonal antibodies against CD 68 and major histocompatibility complex class II antigens were observed around the massive amyloid deposits [31].

Co-localisations of CD68

• Vascular endothelial growth factor was present in areas of inflammation and colocalized with the CD68 stain primarily in the calcified rheumatic valves [32].
• PAPP-A expression in cells of granulation tissue colocalized with alpha-smooth actin staining of myofibroblasts and new blood vessels as well as with CD68 staining of macrophages and was associated with the compact, newly synthesized collagen of the healing wound [33].
• FcRn colocalized in vivo with macrosialin (CD68) and Ncl-Macro, two macrophage markers, in the lamina propria of human small intestine [34].

Regulatory relationships of CD68

• Double-staining techniques revealed that CC chemokine receptor-expressing cells were primarily CD68-positive [35].
• Fibroblasts and about 50% of the CD68 positive macrophages expressed RECK [36].
• The percentage of ICAM-1-expressing cells correlated significantly (P < 0.001) with the percentage of CD68-positive macrophages, but not with CD3- and CD22-positive lymphocytes [37].
• Consecutive tissue sections were stained for CCR5, CD3, and CD68 to define the leukocyte subtype expressing CCR5 in CP [38].
• Nuclear p53 was expressed in CD68-positive cells and smooth muscle cells in 16 of the 18 inflamed arteries [39].

Other interactions of CD68

• Freshly isolated CD34+ CB cells were negative for LZ and LF, and only small proportions expressed MPO (4% +/- 2%) or CD68 (3% +/- 1%) [40].
• Conversely, brain-derived macrophages did not express antigens CD4, CD14, or CD68/Ki-M6, which are easily detected on freshly isolated monocytes [41].
• Double immunostaining showed no coexpression of BMPR-positive cells with CD68, CD34, or CD3 [42].
• Double-immunolabelling for poly(ADP-ribose) and markers of neuronal, astrocytic and microglial differentiation (MAP2, GFAP and CD68, respectively) showed many of the cells containing poly(ADP-ribose) to be neurons [43].
• These data suggest that beta2GPI can bind cells that fail to maintain membrane lipid asymmetry and generate a specific bridging moiety that is recognized for clearance by a phagocyte receptor that is distinct from CD36, CD68, and CD14 [44].

Analytical, diagnostic and therapeutic context of CD68

• Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins [19].
• The combination of in situ hybridization for IL-10 and CD68 immunostaining revealed that only cells of the microglia/macrophage lineage produced IL-10 mRNA [45].
• They expressed cell surface HLA-ABC, HLA-DR, CD45, as well as CD68 intracellularly, as detected by flow cytometry, confirming their macrophage lineage [46].
• Protein was quantitatively assessed by ELISA in cell culture supernatants, and cells expressing IL-10 were determined by a combination of immunohistochemistry for CD68 (specific for microglia/macrophage lineage) and IL-10 in situ hybridization [45].
• METHODS: TdT-mediated dUTP nick end-labelling (TUNEL) of DNA breaks complemented immunoperoxidase staining for CD68 or LCA as the specific cell markers [47].

References