Leukocyte Membrane Enzymes Play the Cell Adhesion Game.

For a long time, proteins with enzymatic activity have not been usually considered to carry out other functions different from catalyzing chemical reactions within or outside the cell. Nevertheless, in the last few years several reports have uncovered the participation of numerous enzymes in other processes, placing them in the category of moonlighting proteins. Some moonlighting enzymes have been shown to participate in complex processes such as cell adhesion. Cell adhesion plays a physiological role in multiple processes: it enables cells to establish close contact with one another, allowing communication; it is a key step during cell migration; it is also involved in tightly binding neighboring cells in tissues, etc. Importantly, cell adhesion is also of great importance in pathophysiological scenarios like migration and metastasis establishment of cancer cells. Cell adhesion is strictly regulated through numerous switches: proteins, glycoproteins and other components of the cell membrane. Recently, several cell membrane enzymes have been reported to participate in distinct steps of the cell adhesion process. Here, we review a variety of examples of membrane bound enzymes participating in adhesion of immune cells.

Dipeptidyl peptidase IV and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVE: Dipeptidyl peptidase IV (DPP-IV) is not only important in beta-cell function but also has proinflammatory actions. We aimed to investigate whether it could act as a link between low-grade chronic inflammation and diabetes. RESEARCH DESIGN AND METHODS: Using a case-cohort design, we followed 546 middle-aged individuals who developed diabetes and 538 who did not over approximately 9 years within the Atherosclerosis Risk in Communities study. RESULTS: In weighted analyses, the correlation between DPP-IV levels and anthropometric, inflammatory, or metabolic variables was minimal (Spearman correlations <0.11). Those who developed diabetes had mean DPP-IV values similar to those who did not (P = 0.18). Individuals in the highest quartile of DPP-IV were not at greater risk of diabetes (hazard ratio 0.88 [95% CI 0.62-1.24]) in Cox proportional hazards models adjusting for age, sex, race, study center, and multiple additional diabetes risk factors. CONCLUSIONS: Fasting DPP-IV levels do not appear to predict incident diabetes.

Streptokinase promotes development of dipeptidyl peptidase IV (CD26) autoantibodies after fibrinolytic therapy in myocardial infarction patients.

Dipeptidyl peptidase IV (DPP IV) (CD26) plays a critical role in the modulation and expression of autoimmune and inflammatory diseases. We recently reported that sera from patients with rheumatoid arthritis and systemic lupus erythematosus contained low levels of DPP IV and high titers of anti-DPP IV autoantibodies of the immunoglobulin A (IgA) and IgG classes and found a correlation between the low circulating levels of DPP IV and the high titers of anti-DPP IV autoantibodies of the IgA class. Since streptokinase (SK) is a potent immunogen and binds to DPP IV, we speculated that patients with autoimmune diseases showed higher DPP IV autoantibody levels than healthy controls as a consequence of an abnormal immune stimulation triggered by SK released during streptococcal infections. We assessed this hypothesis in a group of patients suffering from acute myocardial infarction, without a chronic autoimmune disease, who received SK as part of therapeutic thrombolysis. Concomitant with the appearance of anti-SK antibodies, these patients developed anti-DPP IV autoantibodies. These autoantibodies bind to DPP IV in the region which is also recognized by SK, suggesting that an SK-induced immune response is responsible for the appearance of DPP IV autoantibodies. Furthermore, we determined a correlation between high titers of DPP IV autoantibodies and an augmented clearance of the enzyme from the circulation. Serum levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) increased significantly after 30 days of SK administration, while the levels of soluble IL-2 receptor remained unchanged during the same period, suggesting a correlation between the lower levels of circulating DPP IV and higher levels of TNF-alpha and IL-6 in serum in these patients.