Sofie Struyf

Amino-terminal Truncation of Chemokines by CD26/Dipeptidyl- peptidase IV

Chemokines are key players in inflammation and infection. Natural forms of the C-X-C chemokine granulocyte chemotactic protein-2 (GCP-2) and the C-C chemokine regulated on activation normal T cell expressed and secreted (RANTES), which miss two NH2-terminal residues, including a Pro in the penultimate position, have been isolated from leukocytes or tumor cells. In chemotaxis and intracellular calcium mobilization assays, the truncation caused a reduction in the specific activity of RANTES but not of GCP-2. The serine protease CD26/dipeptidyl-peptidase IV (CD26/DPP IV) could induce this observed NH2-terminal truncation of GCP-2 and RANTES but not that of the monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3. No significant difference in neutrophil activation was detected between intact and CD26/DPP IV-truncated GCP-2. In contrast to intact natural RANTES(1–68), which still chemoattracts monocytes at 10 ng/ml, CD26/DPP IV-truncated RANTES(3–68) was inactive at 300 ng/ml and behaved as a natural chemotaxis inhibitor. Compared with intact RANTES, only a 10-fold higher concentration of RANTES(3–68) induced a significant Ca2+ response. Furthermore, RANTES(3–68) inhibited infection of mononuclear cells by an M-tropic HIV-1 strain 5-fold more efficiently than intact RANTES. Thus, proteolytic processing of RANTES by CD26/DPP IV may constitute an important regulatory mechanism during anti-inflammatory and antiviral responses.

Circulating fibrocytes contribute to the myofibroblast population in proliferative vitreoretinopathy epiretinal membranes

Background/aims: Fibrocytes, circulating cells that co-express markers of haematopoietic stem cells, leucocytes and fibroblast products, traffic to sites of tissue injury, differentiate into myofibroblasts and contribute to wound healing and fibrosis. We investigated the presence of fibrocytes and the expression of their chemotactic pathways CCL21/CCR7 and CXCL12/CXCR4 in proliferative vitreoretinopathy (PVR) epiretinal membranes. Methods: Sixteen membranes were studied by immunohistochemical techniques. Results: Cells expressing α-smooth-muscle actin (α-SMA), a marker of differentiation of fibrocytes into myofibroblasts, were present in all membranes. Cells expressing the haematopoietic stem-cell antigen CD34, the leucocyte common antigen CD45, CCR7, CXCR4, CCL21 and CXCL12 were noted in 50%, 75%, 68.8%, 100%, 80% and 93.8% of the membranes, respectively. Double immunohistochemistry indicated that all cells expressing CD34, CD45, CCR7, CXCR4, CCL21 and CXCL12 co-expressed α-SMA. The number of cells expressing CD34 correlated significantly with the numbers of cells expressing CXCL12 (rsu200a=u200a0.567; pu200a=u200a0.022) and CCL21 (rsu200a=u200a0.534; pu200a=u200a0.04). Conclusions: Circulating fibrocytes may function as precursors of myofibroblasts in PVR membranes.

Expression of T lymphocyte chemoattractants and activation markers in vernal keratoconjunctivitis

Background/aims: T lymphocytes are present in increased numbers in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and their activation has a central role in the pathogenesis of the chronic allergic inflammatory reactions seen in VKC. The aims of this study were to examine the expression of three recently described potent T lymphocyte chemoattractants, PARC (pulmonary and activation regulated chemokine), macrophage derived chemokine (MDC), and I-309, the MDC receptor CCR4, and T lymphocyte activation markers, CD25, CD26, CD62L, CD71, and CD30, and to correlate them with the counts of CD3+ T lymphocytes in the conjunctiva of patients with VKC. Method: Conjunctival biopsy specimens from 11 patients with active VKC, and eight control subjects were studied by immunohistochemical techniques using a panel of monoclonal and polyclonal antibodies directed against PARC, MDC, I-309, CCR4, CD25, CD26, CD62L, CD71, and CD30. The numbers of positively stained cells were counted. The phenotype of inflammatory cells expressing chemokines was examined by double immunohistochemistry. Results: In the normal conjunctiva, vascular endothelial cells in the upper substantia propria showed weak immunoreactivity for CD26. There was no immunoreactivity for the other antibodies. VKC specimens showed inflammatory cells expressing PARC, MDC, and I-309. The numbers of PARC+ inflammatory cells were higher than the numbers of MDC+ and I-309+ inflammatory cells and the mean values of the three groups differed significantly (17.0 (SD 10.1); 9.5 (9.9), and 4.3 (7.9), respectively, p = 0.0117, ANOVA). The numbers of PARC+ inflammatory cells had the strongest correlation with the numbers of CD3+ T lymphocytes. Few CCR4+ inflammatory cells were observed in only three specimens. Double immunohistochemistry revealed that all inflammatory cells expressing chemokines were CD68+ monocytes/macrophages. The numbers of CD25+ T lymphocytes were higher than the numbers of CD26+, CD62L+, CD71+, and CD30+ T lymphocytes and the mean values of the five groups differed significantly (46.2 (27.9), 30.7 (16.0), 20.1 (8.6), 7.8 (7.7), and 6.5 (4.0), respectively, p <0.001, ANOVA). The numbers of CD25+ T lymphocytes had the strongest correlation with the numbers of CD3+ T lymphocytes. Conclusion: These results suggest a potential role for PARC, MDC, and I-309 in attracting T lymphocytes into conjunctiva in VKC. T lymphocytes in VKC are activated and express several activation markers which might contribute to the pathogenesis of VKC.

PF4V1 (Platelet Factor 4 Variant 1)

Review on PF4V1 (Platelet Factor 4 Variant 1), with data on DNA, on the protein encoded, and where the gene is implicated.

PF4 (platelet factor 4)

Review on PF4, with data on DNA/RNA, on the protein encoded and where the gene is implicated.