Cathepsin K – a marker of macrophage differentiation?

Sarcoidosis is a chronic disease of unknown etiology characterized by the formation of non-necrotizing epithelioid granulomas in various organs , especially in the lungs. The lack of an adequate animal model reflecting the pathogenesis of the human disease is one of the major impediments in studying sarcoidosis. In this report , we describe ApoE ؊/؊ mice on a cholatecontaining high-fat diet that exhibit granulomatous lung inflammation similar to human sarcoidosis. Histological analysis revealed well-defined and non-necrotizing granulomas in about 40% of mice with the highest number of granulomas after 16 weeks on a cholate-containing high-fat diet. Granulomas contained CD4؉ and CD8 ؉ T cells , and the majority of the cells in granulomas showed immunoreactivity for the macrophage marker Mac-3. Cells with morphological features of epithelioid cells expressed angiotensinconverting enzyme , osteopontin , and cathepsin K, all characteristics of epithelioid and giant cells in granulomas of human sarcoidosis. Giant cells and nonspecific inclusions such as Schaumann's bodies and crystalline deposits were also detected in some lungs. Granulomatous inflammation resulted in progressive pulmonary fibrosis. Removal of cholate from the diet prevented the formation of lung granulomas. The observed similarities between the analyzed mouse lung granulomas and granulomas of human sarcoidosis , as well as the chronic disease character leading to fibrosis , suggest that this mouse model might be a useful tool to study sarcoidosis.

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“…20 Our results support this notion because cathepsin K immunoreactivity in epithelioid and giant cells was highly elevated in lung granulomas.…”

Section: Discussionsupporting

confidence: 81%

ApoE-Deficient Mice on Cholate-Containing High-Fat Diet Reveal a Pathology Similar to Lung Sarcoidosis

Samokhin

Bühling

Theissig

et al. 2010

The American Journal of Pathology

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“…However, when the microglial cells are activated, many of these molecules are up-regulated and these cells in the adult nervous tissue resemble those observed during development (Streit et al, 1999). Indeed, activated microglia secrete cathepsin B in cell cultures (Kingham and Pocock, 2001), and cathepsins are upregulated in activated macrophages under physiological, experimental, and pathological conditions (Buhling et al, 2001;Moon et al, 2008;de Nooijer et al, 2009). Overall, these findings suggest that cathepsins may be considered to be markers for macrophages and microglial precursors during normal development, and also markers of macrophage/microglia activation under physiological, experimental, and pathological conditions in the adult tissues.…”

Section: Cathepsin B and D Expression In Macrophages And Microglial Pmentioning

confidence: 99%

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

Bejarano-Escobar

Holguín-Arévalo

Montero

et al. 2011

Developmental Dynamics

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Here, we show a detailed chronotopographical analysis of cathepsin B and D expression during development of the mouse visual system. Both proteases were detected in large rounded/ameboid cells usually located in close relationship with prominent sites of extensive physiological cell death. In concordance with their morphological features and topographical distribution, we demonstrate that expressing cells corresponded with macrophages and microglial precursors. We found that as microglial precursors differentiated the expression of both cathepsins was down-regulated. Of interest, cathepsin B and D transcripts were never observed in degenerating cells. Our findings point to a role for cathepsin D and B in cell debris degradation after apoptotic processes rather than promoting cell death, as proposed for other developmental models. Additionally their pattern of expression suggests a role in the maturation of the microglial precursors.

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“…Currently, cathepsin K is one of the most potent elastases and also has collagenolytic activity. Cathepsin K has been previously shown to reside in macrophages, 39,40 fibroblasts, 36 and bronchiolar epithelial cells. 41 In the current study, the majority of cathepsin K was localized to the interstitial and CD45-positive cells as determined by immunofluorescence whereas minimal reactivity was observed in the bronchiolar epithelium.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiles Reveal Increased mClca3 (Gob5) Expression and Mucin Production in a Murine Model of Asbestos-Induced Fibrogenesis

Sabo‐Attwood

Ramos-Niño

Bond

et al. 2005

The American Journal of Pathology

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To elucidate genes important in development or repair of asbestos-induced lung diseases, gene expression was examined in mice after inhalation of chrysotile asbestos for 3, 9, and 40 days. We identified changes in the expression of genes linked to proliferation (cyclin B2, CDC20, and CDC28 protein kinase regulatory subunit 2), inflammation (CCL9, CCL6, complement component 1, chitinase3-like 3, TNF superfamily member 10, and IL-1B), and matrix remodeling (MMP12, MMP3, integrin ␣X, and cathepsins K, Z, B, and S). The most highly induced gene at all time points was mclca3 (gob5), a putative calcium-activated chloride channel involved in the regulation of mucus production and/or secretion. Using histochemistry, we demonstrated accumulation of mucus and increased mClca3 protein in the bronchiolar epithelium of asbestos-exposed mice at all time points but peaking at 9 days. Cytokine levels (interleukin-1␤, interleukin-4, interleukin-6) in bronchoalveolar lavage fluid also increased at 9 days, suggesting Th2-mediated immunity may play a role in asbestosinduced mucus production. In contrast, levels of cathepsin K, a potent elastase, increased between 3 and 40 days at both the mRNA and protein levels, localizing primarily in CD45-positive leukocytes and interstitial cells. Identification of genes involved in lung injury and remodeling after asbestos exposure could aid in defining mechanisms of airborne particulate-

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Cathepsin K – a marker of macrophage differentiation?

Cited by 27 publications

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ApoE-Deficient Mice on Cholate-Containing High-Fat Diet Reveal a Pathology Similar to Lung Sarcoidosis

ApoE-Deficient Mice on Cholate-Containing High-Fat Diet Reveal a Pathology Similar to Lung Sarcoidosis

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

Gene Expression Profiles Reveal Increased mClca3 (Gob5) Expression and Mucin Production in a Murine Model of Asbestos-Induced Fibrogenesis

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