Karolina Jankovicova

SCAVENGER RECEPTOR CD163 AND ITS BIOLOGICAL FUNCTIONS

CD163 is a member of scavenger receptor super family class B of the first subgroup. It is mapped to the region p13 on chromosome 12. Five different isoforms of CD163 have been described, which differ in the structure of their cytoplasmic domains and putative phosporylation sites. This scavenger receptor is selectively expressed on cells of monocytes and macrophages lineage exclusively. CD163 immunological function is essentially homeostatic. It also has other functions because participates in adhesion to endothelial cells, in tolerance induction and tissues regeneration. Other very important function of CD163 is the clearance of hemoglobin in its cell-free form and participation in anti-inflammation in its soluble form, exhibiting cytokine-like functions. We review the biological functions of CD163 which have been discovered until now. It seems apparent from this review that CD163 scavenger receptor can be used as biomarker in different diseases and as a valuable diagnostic parameter for prognosis of many diseases especially inflammatory disorders and sepsis.

Biological prognostic markers in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemic disease of adults in the Western world. It is remarkable by an extraordinary heterogeneity of clinical course with overall survival ranging from several months to more than 15 years. Classical staging sytems by Rai and Binet, while readily available and useful for initial assessment of prognosis, are not able to determine individual patients ongoing clinical course of CLL at the time of diagnosis, especially in early stages. Therefore, newer biological prognostic parameters are currently being clinically evaluated. Mutational status of variable region of immunoglobulin heavy chain genes (IgVH), cytogenetic aberrations, and both intracellular ZAP- 70 and surface CD38 expression are recognized as parameters with established prognostic value. Molecules regulating the process of angiogenesis are also considered as promising markers. The purpose of this review is to summarize in detail the specific role of these prognostic factors in chronic lymphocytic leukemia.

Early Expression of FcRI (CD64) on Monocytes of Cardiac Surgical Patients and Higher Density of Monocyte Anti-Inflammatory Scavenger CD163 Receptor in “On-Pump” Patients

Objective. Activation of innate immunity cells is inseparably linked to cardiac surgical operation. The aim of this study was to assess the kinetics in the expression of receptor for Fc part of IgG, FcγRI (CD64), and scavenger receptor CD163 on peripheral blood cells of cardiac surgical patients and to examine the effect of cardiac bypass as a separable influence on the systemic acute inflammatory response. Methods. Forty patients, twenty in each group, were randomly assigned to CABG surgery performed either with “on-pump” or without “off-pump” cardiopulmonary bypass. Standardized quantitative flow cytometry method was used to determine the expression of surface markers. Results. The density of CD64 molecule on monocytes reached maximum on the 1st postoperative day (P<.001) whereas the peak for CD64 molecule expression on granulocytes was postponed to the 3rd postoperative day (P<.001). The expression of CD163 scavenger molecule on monocytes reached maximum on the 1st postoperative day (P<.001). The density of CD163 molecule on monocytes on the 1st postoperative day is significantly higher in “on-pump” patients in comparison with “off-pump” patients (P<.001). Conclusion. In cardiac surgical patients the expression of activation marker FcγR1 (CD64) on monocytes is increased earlier in comparison with granulocytes in both “on-pump” and “off-pump” patients. The expression of scavenger molecule CD163 on monocytes is significantly higher in “on-pump” patients.

Serum level of sCD163, a soluble receptor for hemoglobin, is influenced by cardiac surgery

Background:The scavenger receptor for complexes hemoglobin-haptoglobin (CD163), which is expressed on monocytes/ macrophages, is shed to the body fluids in a soluble form (sCD163). Objectives: To evaluate the dynamics of sCD163 in the blood of patients undergoing cardiac surgery. Patients and Methods: Sixty-one adult patients who underwent coronary artery bypass grafting (CABG) were enrolled in the study. They were assigned to undergo CABG using either cardiopulmonary bypass (CPB), “on-pump”, (22 patients), modified CPB, mini “on-pump”, (17 patients) or without CPB, “off-pump”, (22 patients) surgery. Serum levels of sCD163 in venous blood samples taken before and after surgery, and during an early postoperative period, were evaluated by Macro 163TM diagnostic kit (IQ Products, Groningen, NL). Results: Compared to the preoperative levels (“on-pump”; 344 ng/mL, “off-pump”; 314.5 ng/mL, mini-invasive “on-pump”; 336.5 ng/mL) serum levels were elevated at the finish of surgery, reaching maximum at the 1st postoperative day (“onpump”; 658 ng/mL; p<0.05, “off-pump”; 810.5 ng/mL; p<0.01; mini-invasive “on-pump”; 663 ng/mL; non-significant). No significant differences regarding the serum levels of sCD163 between different surgical approaches were found. Conclusion: Serum level of sCD163 scavenger molecule for hemoglobin is elevated at the end of surgery and at the 1st postoperative day, being little influenced by cardiopulmonary bypass.

Lipopolysaccharide Binding Protein and sCD14 are Not Produced as Acute Phase Proteins in Cardiac Surgery

Objectives. The changes in the serum levels of lipopolysaccharide binding protein (LBP) and sCD14 during cardiac surgery were followed in this study. Design. Thirty-four patients, 17 in each group, were randomly assigned to coronary artery bypass grafting surgery performed either with (“on-pump”) or without (“off-pump”) cardiopulmonary bypass. LBP and sCD14 were evaluated by ELISA. Results. The serum levels of LBP were gradually increased from the 1st postoperative day and reached their maximum on the 3rd postoperative day in both “on-pump” and “off-pump” patients (30.33±9.96 μg/mL; 37.99±16.58 μg/mL), respectively. There were no significant differences between “on-pump” and “off-pump” patients regarding LBP. The significantly increased levels of sCD14 from the 1st up to the 7th postoperative day in both “on-pump” and “off-pump” patients were found with no significant differences between these groups. No correlations between LBP and sCD14 and IL-6, CRP and long pentraxin PTX3 levels were found. Conclusions. The levels of LBP and sCD14 are elevated in cardiac surgical patients being similar in both groups. These molecules are not produced as acute phase proteins in these patients.

Expression of CD200/CD200R regulatory molecules on granulocytes and monocytes is modulated by cardiac surgical operation

Aims: Cardiac surgical operation is inseparably linked to the induction of an inflammatory response. Both humoral and cellular regulatory mechanisms are operating to maintain body homeostasis. We followed the changes in the expression of CD200/CD200R regulatory molecules on monocytes and granulocyte of cardiac surgical patients operated on using either standard (OP) or modified “mini-invasive” cardiopulmonary bypass (MOP). Methods: Expression of CD200/CD200R regulatory molecules was determined by flow cytometry. Results: The expression of CD200R on granulocytes was increased after surgery in both groups of patients, but the increase was statistically significant only in OP patients (p<0.01). At this time point, there was a significant difference in CD200R expression on granulocytes when comparing OP to MOP patients, being higher in the former group (p<0.01). The expression of CD200R on monocytes was diminished after surgery and during an early postoperative period in both groups of patients. The expression of CD200 on monocytes was significantly diminished after surgery in both groups (p<0.01). Nonetheless, we observed an increase in CD200 expression in OP patients at the 3rd postoperative day. There was a statistically significantly increased CD200 expression on monocytes of OP patients (p<0.001) at the 3rd postoperative day when we compared OP and MOP groups. The expression of CD200 on granulocytes was significantly higher after surgery and at the 3rd postoperative day in OP when compared to MOP patients. Conclusions: CD200R expression on granulocytes was significantly increased, while CD200 and CD200R expression on monocytes was decreased after cardiac surgery.

Significant change in ZAP-70 expression during the course of chronic lymphocytic leukemia.

Introduction:  It is widely accepted that expression of ZAP‐70 in chronic lymphocytic leukemia (CLL) remains stable in time. However, data supporting this notion are surprisingly scarce. Therefore, we assessed expression of ZAP‐70 in serial samples taken during the course of the disease.

Interferon gamma receptor expression on granulocytes of cardiac surgical patients is modulated differently by the type of cardiopulmonary bypass used

Aims: To follow the IFNγ receptor expression on monocytes and granulocytes of cardiac surgical patients with respect to the type of cardiopulmonary bypass (CPB). Methods: Expression of IFNγ receptor on monocytes and granulocytes of 26 cardiac surgical patients operated with the use of either “standard” or “miniaturised” CPB was determined by flow cytometry. Results: The significant increase in IFNγ receptor expression on monocytes on the 1st and on the 3rd postoperative days was revealed in both groups of patients (p<0.001) irrespective of the type of CPB used, being non-significantly different between groups. In contrast, the expression of IFNγ on granulocytes displayed significant differences in terms of the CPB used. Whereas, in “standard” CPB patients, granulocyte INFγ receptor expression reached its maximum immediately after surgery (p<0.01), in “miniivasive” CPB patients, the peak in INFγ receptor expression was postponed to the 1st postoperative day (p<0.05). Statistically significantly higher IFNγ receptor expression on granulocytes was found in “standard” CPB patients (p<0.05). Conclusion: Compared to “miniaturised” CPB patients, the significantly higher IFNγ receptor expression on granulocytes was found in “standard” CPB patients (p<0.05) on the 1st postoperative day.

TLR2 in Pleural Fluid Is Modulated by Talc Particles during Pleurodesis

The aim of this study was to examine the role of TLR2 molecule in pleural space during thoracoscopic talc pleurodesis period in patients with malignant pleural effusion. We analyzed TLR2 molecule in soluble form as well as on membrane of granulocytes in pleural fluid. Pleural fluid examination was done at three intervals during pleurodesis procedure: 1st—before the thoracoscopic procedure, 2nd—2 hours after the terminating thoracoscopic procedure with talc insufflation, 3rd—24 hours after the thoracoscopic procedure. We reported significant increase of soluble TLR2 molecule in pleural fluid effusion during talc pleurodesis from preoperative value. This increase was approximately 8-fold in the interval of 24 hours. The changes on granulocyte population were quite different. The mean fluorescent intensity of membrane TLR2 molecule examined by flow cytometry on granulocyte population significantly decreased after talc exposure with comparison to prethoracoscopic density. To estimate the prognostic value of TLR2 expression in pleural fluid patients were retrospectively classified into either prognostically favourable or unfavourable groups. Our results proved that patients with favourable prognosis had more than 3-fold higher soluble TLR2 level in pleural fluid early, 2 hours after talc pleurodesis intervention.

The dynamics of selected local inflammatory markers to talc in the treatment of malignant pleural effusions

BACKGROUND Malignant pleural effusions accumulate in the space between the visceral (inner) layer covering the lungs and the parietal (outer) layer covering the chest wall. Larger effusions compress the pulmonary parenchyma resulting in increasing dyspnoea. Treatment is always local and palliative. Among others, chemical pleurodesis using talc can be performed in selected patients. Talc is hydrated magnesium silicate (chemically H₂Mg₃(SiO₃)₄) and has been used for pleurodesis since 1935. Videothoracoscopic talc powder insufflation (talc poudrage) is the most effective.However, markers of inflammatory reactions to extraneous substances like talc are not fully understood. The aim of this study was to assess the course of local inflammatory changes in the pleural cavity after talc insufflation. METHODS The Department of Cardiac Surgery of the Faculty of Medicine and University Hospital in Hradec Kralove, treated 47 patients aged 65 on average; 29 males and 18 females with proven recurrent malignant pleural effusion of various aetiologies from January 2009 to December 2010. They were retrospectively divided into group A (40 patients) without recurring effusion, and group B (7 patients) with recurring effusion and the need for thoracentesis or chest drainage during the 9-month monitoring. RESULTS Major findings were made in soluble forms of cell receptors. Group B showed statistically higher levels of the anti-inflammatory form of sCD-163 receptor in pleural fluid before the talc poudrage. This showed limited ability to create an adequate inflammatory response to external stimuli. This group also showed lower levels of the inflammatory form of sTLR-2 receptor immediately after the talc insufflation. This revealed low local reactivity to external stimuli. The effect of the treatment was not influenced by morphologic tumour type. No statistically significant differences in postoperative complications were found. This confirmed the safety of both videothoracoscopy and treatment. CONCLUSIONS There was no correlation between the type of malignant affection and the outcome of the chemical pleurodesis. Patients with relapsing effusion have higher values of concentration of anti-inflammatory sCD-163 in pleural fluid even before the application of talc, and lower levels of concentration of inflammatory sTLR-2 immediately after application of talc.