Saskia Van Blokland - Academia.edu (original) (raw)

Uploads

Papers by Saskia Van Blokland

Research paper thumbnail of Apoptosis and apoptosis-related molecules in the submandibular gland of the nonobese diabetic mouse model for Sjögren's syndrome: limited role for apoptosis in the development of sialoadenitis

Laboratory investigation; a journal of technical methods and pathology, 2003

Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the e... more Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the exocrine glands. Pathogenetic aspects of the disease can be studied in the nonobese diabetic (NOD) mouse strain, a spontaneous model for Sjögren's syndrome. Apoptosis may play a role in the initation phase and in the effector phase of autoimmune diseases. Here, we have examined the role of apoptosis in the development of sialoadenitis in the NOD mouse. Apoptotic cells and the expression of apoptosis-related molecules were studied in submandibular glands (SMG) of NOD and NOD-scid mice before and after the onset of sialoadenitis. Numbers of apoptotic cells were not increased as compared with control mice, at any age. By immunohistochemistry, we demonstrated increased expression of Fas, Fas ligand (FasL), and bcl-2 on SMG epithelial cells of NOD and NOD-scid mice, as early as 3 days of age. mRNA expression of Fas and FasL was also examined in SMG by RQ-PCR. Low-level expression of Fas an...

Research paper thumbnail of Proapoptosis and Antiapoptosis-Related Molecules During Postnatal Pancreas Development in Control and Nonobese Diabetic Mice: Relationship with Innervation

Laboratory Investigation, 2003

The mouse pancreas, an immature organ at birth, reaches its adult size and morphology after weani... more The mouse pancreas, an immature organ at birth, reaches its adult size and morphology after weaning (3 weeks of age). Around this time, apoptotic phenomena and various types of macrophages are normally present. During development, Fas-Fas ligand (FasL) interactions are known to play a role in apoptotic events involved in tissue remodeling and elimination of damaged cells, and macrophages are routinely observed near apoptotic cells. Apoptosis and Fas-FasL interactions are also thought to be involved in the pathogenesis of autoimmune diseases, particularly type 1 diabetes (T1D). Therefore, we used early postnatal mouse pancreata from three control strains (C57BL/6, DBA/2, BALB/c) and from two strains with the nonobese diabetic (NOD)-related genetic background (the spontaneous T1D NOD model and the lymphocyte-deficient NODscid strain) to study apoptotic phenomena together with the molecular and immunohistochemical expression of proapoptosis (Fas, FasL) and antiapoptosis (Bcl-2) proteins. First, although no major difference in the numbers of total pancreatic apoptotic cells was noted among strains, significantly more FasL ϩ expression was detected immunohistochemically in mice with the NOD genetic background than in control pancreata from birth to 1 month of age. Second, FasL ϩ , Fas ϩ , and Bcl-2 ϩ structures seemed to be associated with innervation, regardless of the strain and age. Third, in control and NOD strains, nerves (identified by immunohistochemical labeling of peripherin or neurofilament 200), were often observed in periductular and peri-insular areas. Finally, some peripherin-positive nerves expressed the interferon-inducible protein-10 chemokine, and various types of macrophages were found to be in close proximity. These data highlight an overlooked, innervation-related aspect of normal mouse postnatal pancreas development with possible implications in T1D pathogenesis.

Research paper thumbnail of Two Different Types of Sialoadenitis in the NOD- and MRL/lpr Mouse Models for Sjögren’s Syndrome: A Differential Role for Dendritic Cells in the Initiation of Sialoadenitis?

Laboratory Investigation, 2000

Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal gla... more Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjö gren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/lpr mouse, can be used as models for Sjö gren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/lpr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/lpr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/lpr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjö gren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients. (Lab Invest 2000, 80:575-585). S jö gren's syndrome is a systemic autoimmune dis

Research paper thumbnail of In Vitro Insertion and Assembly of Outer Membrane Protein PhoE of Escherichia coli K-12 into the Outer Membrane. ROLE OF TRITON X-100

Journal of Biological Chemistry, 1996

Research paper thumbnail of Pathogenesis of Sjögren's Syndrome: Characteristics of Different Mouse Models for Autoimmune Exocrinopathy

Clinical Immunology, 2002

Research paper thumbnail of Two different types of sialoadenitis in the NOD-and MRL/lpr mouse models for Sjögren's syndrome: a differential role for dendritic cells in the initiation of sialoadenitis?

Laboratory …, 2000

Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal gla... more Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjö gren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/lpr mouse, can be used as models for Sjö gren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/lpr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/lpr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/lpr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjö gren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients. (Lab Invest 2000, 80:575-585). S jö gren's syndrome is a systemic autoimmune dis

Research paper thumbnail of Professional Antigen Presenting Cells in Minor Salivary Glands in Sjögren’s Syndrome: Potential Contribution to the Histopathological Diagnosis?

Laboratory Investigation, 2000

Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the saliv... more Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the salivary and lacrimal glands. We have shown that dendritic cells (DC) infiltrate the submandibular gland of the nonobese diabetic (NOD) mouse, a mouse model for Sjögren's syndrome, before lymphocytic infiltration, suggesting that these antigen-presenting cells (APC) may play a role in the initiation of Sjögren's syndrome. In later stages, DC and macrophages also form an important part of the infiltrate of the NOD sialoadenitis. To find out if DC and macrophages form part of the infiltrate in Sjögren's syndrome as well, and to determine whether they may be useful in the histopathological diagnosis of Sjögren's syndrome, we studied their presence in minor salivary glands (MSG) of patients with Sjögren's syndrome and patients with focal lymphocytic sialoadenitis (FLS), but without clinical or serological criteria of Sjögren's syndrome. Immunohistochemistry was applied, followed by semiquantitative analysis. DC and macrophages were present in all MSG; however, there were clear differences in marker expression between Sjögren's syndrome and FLS, on the one hand, and control tissue, on the other hand. CD1a ϩ DC and RFD9 ϩ macrophages were mainly observed in MSG in which a focal lymphocytic infiltrate was present. In fact, the diffuse presence of single CD1a ϩ DC and RFD9 ϩ macrophages correlated closely with the presence of a focal lymphocytic infiltrate in the MSG. This indicates that these cells could be of help during the evaluation of a MSG. Because the detection of APC is technically less cumbersome than a focal score, this parameter may perhaps replace the focal score in the histopathological diagnosis of Sjögren's syndrome. This study therefore prompts further investigation focusing on the presence of CD1a ϩ and RFD9 ϩ cells in the MSG of a large cohort of

Research paper thumbnail of Apoptosis and apoptosis-related molecules in the submandibular gland of the nonobese diabetic mouse model for Sjögren's syndrome: limited role for apoptosis in the development of sialoadenitis

Laboratory investigation; a journal of technical methods and pathology, 2003

Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the e... more Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the exocrine glands. Pathogenetic aspects of the disease can be studied in the nonobese diabetic (NOD) mouse strain, a spontaneous model for Sjögren's syndrome. Apoptosis may play a role in the initation phase and in the effector phase of autoimmune diseases. Here, we have examined the role of apoptosis in the development of sialoadenitis in the NOD mouse. Apoptotic cells and the expression of apoptosis-related molecules were studied in submandibular glands (SMG) of NOD and NOD-scid mice before and after the onset of sialoadenitis. Numbers of apoptotic cells were not increased as compared with control mice, at any age. By immunohistochemistry, we demonstrated increased expression of Fas, Fas ligand (FasL), and bcl-2 on SMG epithelial cells of NOD and NOD-scid mice, as early as 3 days of age. mRNA expression of Fas and FasL was also examined in SMG by RQ-PCR. Low-level expression of Fas an...

Research paper thumbnail of Proapoptosis and Antiapoptosis-Related Molecules During Postnatal Pancreas Development in Control and Nonobese Diabetic Mice: Relationship with Innervation

Laboratory Investigation, 2003

The mouse pancreas, an immature organ at birth, reaches its adult size and morphology after weani... more The mouse pancreas, an immature organ at birth, reaches its adult size and morphology after weaning (3 weeks of age). Around this time, apoptotic phenomena and various types of macrophages are normally present. During development, Fas-Fas ligand (FasL) interactions are known to play a role in apoptotic events involved in tissue remodeling and elimination of damaged cells, and macrophages are routinely observed near apoptotic cells. Apoptosis and Fas-FasL interactions are also thought to be involved in the pathogenesis of autoimmune diseases, particularly type 1 diabetes (T1D). Therefore, we used early postnatal mouse pancreata from three control strains (C57BL/6, DBA/2, BALB/c) and from two strains with the nonobese diabetic (NOD)-related genetic background (the spontaneous T1D NOD model and the lymphocyte-deficient NODscid strain) to study apoptotic phenomena together with the molecular and immunohistochemical expression of proapoptosis (Fas, FasL) and antiapoptosis (Bcl-2) proteins. First, although no major difference in the numbers of total pancreatic apoptotic cells was noted among strains, significantly more FasL ϩ expression was detected immunohistochemically in mice with the NOD genetic background than in control pancreata from birth to 1 month of age. Second, FasL ϩ , Fas ϩ , and Bcl-2 ϩ structures seemed to be associated with innervation, regardless of the strain and age. Third, in control and NOD strains, nerves (identified by immunohistochemical labeling of peripherin or neurofilament 200), were often observed in periductular and peri-insular areas. Finally, some peripherin-positive nerves expressed the interferon-inducible protein-10 chemokine, and various types of macrophages were found to be in close proximity. These data highlight an overlooked, innervation-related aspect of normal mouse postnatal pancreas development with possible implications in T1D pathogenesis.

Research paper thumbnail of Two Different Types of Sialoadenitis in the NOD- and MRL/lpr Mouse Models for Sjögren’s Syndrome: A Differential Role for Dendritic Cells in the Initiation of Sialoadenitis?

Laboratory Investigation, 2000

Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal gla... more Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjö gren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/lpr mouse, can be used as models for Sjö gren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/lpr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/lpr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/lpr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjö gren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients. (Lab Invest 2000, 80:575-585). S jö gren's syndrome is a systemic autoimmune dis

Research paper thumbnail of In Vitro Insertion and Assembly of Outer Membrane Protein PhoE of Escherichia coli K-12 into the Outer Membrane. ROLE OF TRITON X-100

Journal of Biological Chemistry, 1996

Research paper thumbnail of Pathogenesis of Sjögren's Syndrome: Characteristics of Different Mouse Models for Autoimmune Exocrinopathy

Clinical Immunology, 2002

Research paper thumbnail of Two different types of sialoadenitis in the NOD-and MRL/lpr mouse models for Sjögren's syndrome: a differential role for dendritic cells in the initiation of sialoadenitis?

Laboratory …, 2000

Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal gla... more Sjö gren's syndrome is an autoimmune disease that primarily affects the salivary and lacrimal glands. In these glands, focal lymphocytic infiltrates develop. Little is known about the initiation of this autoimmune disease. Antigen-presenting cells (APC) such as dendritic cells (DC) can play a role in the initiation of autoimmunity. To date, no data on the presence of DC in Sjö gren's syndrome are available. Several mouse strains, the nonobese diabetic (NOD) and the MRL/lpr mouse, can be used as models for Sjö gren's syndrome. We compared the development of sialoadenitis in the submandibular glands (SMG) of NOD and MRL/lpr mice with particular focus on the presence of APC. DC, macrophages, T cells, and B cells in the SMG were studied by means of immunohistochemistry, after which positively stained cells were quantified. NOD-severe combined immunodeficiency (SCID) mice were used to study the presence of APC in the SMG in the absence of lymphocytes. Before lymphocytic infiltration, increased numbers of DC were detected in the SMG of NOD mice compared with those numbers in control mice and MRL/lpr mice, which suggests that DC play a role in the initiation of sialoadenitis in NOD mice. In the SMG of NOD mice, lymphocytic infiltrates organized in time. In MRL/lpr mice, however, lymphocytic infiltrates were already organized at the time of appearance. This organization was lost over time. In conclusion, two types of sialoadenitis are described in two mouse models for Sjö gren's syndrome. Differences exist with regard to early events that may lead to the development of sialoadenitis and to the composition and organization of inflammatory infiltrates. It is possible that different types of sialoadenitis also exist in humans and that the pathogenetic process in both the early and late phases of the autoimmune reaction differs among patients. (Lab Invest 2000, 80:575-585). S jö gren's syndrome is a systemic autoimmune dis

Research paper thumbnail of Professional Antigen Presenting Cells in Minor Salivary Glands in Sjögren’s Syndrome: Potential Contribution to the Histopathological Diagnosis?

Laboratory Investigation, 2000

Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the saliv... more Sjögren's syndrome is an autoimmune disease in which lymphocytic infiltrates develop in the salivary and lacrimal glands. We have shown that dendritic cells (DC) infiltrate the submandibular gland of the nonobese diabetic (NOD) mouse, a mouse model for Sjögren's syndrome, before lymphocytic infiltration, suggesting that these antigen-presenting cells (APC) may play a role in the initiation of Sjögren's syndrome. In later stages, DC and macrophages also form an important part of the infiltrate of the NOD sialoadenitis. To find out if DC and macrophages form part of the infiltrate in Sjögren's syndrome as well, and to determine whether they may be useful in the histopathological diagnosis of Sjögren's syndrome, we studied their presence in minor salivary glands (MSG) of patients with Sjögren's syndrome and patients with focal lymphocytic sialoadenitis (FLS), but without clinical or serological criteria of Sjögren's syndrome. Immunohistochemistry was applied, followed by semiquantitative analysis. DC and macrophages were present in all MSG; however, there were clear differences in marker expression between Sjögren's syndrome and FLS, on the one hand, and control tissue, on the other hand. CD1a ϩ DC and RFD9 ϩ macrophages were mainly observed in MSG in which a focal lymphocytic infiltrate was present. In fact, the diffuse presence of single CD1a ϩ DC and RFD9 ϩ macrophages correlated closely with the presence of a focal lymphocytic infiltrate in the MSG. This indicates that these cells could be of help during the evaluation of a MSG. Because the detection of APC is technically less cumbersome than a focal score, this parameter may perhaps replace the focal score in the histopathological diagnosis of Sjögren's syndrome. This study therefore prompts further investigation focusing on the presence of CD1a ϩ and RFD9 ϩ cells in the MSG of a large cohort of