Purpose: Contact lens (CL) wear challenges the balance of the ocular surface environment by increasing water evaporation and tear osmolarity. Maintaining ocular surface homeostasis during CL wear remains a goal of lens manufacturers and an important consideration for eye care professionals. The purpose of this study was to measure the metabolic activity and inflammatory responses of a transformed human corneal epithelial cell (THCEpiC) line under hyperosmotic conditions in the presence of CL packaging solutions.
View Article and Find Full Text PDFMacrophage antibody (Ab)-dependent cellular phagocytosis (ADCP) is a major cytotoxic mechanism for both therapeutic unconjugated monoclonal Abs (mAbs) such as rituximab and Ab-induced hemolytic anemia and immune thrombocytopenia. Here, we studied the mechanisms controlling the rate and capacity of macrophages to carry out ADCP in settings of high target/effector cell ratios, such as those seen in patients with circulating tumor burden in leukemic phase disease. Using quantitative live-cell imaging of primary human and mouse macrophages, we found that, upon initial challenge with mAb-opsonized lymphocytes, macrophages underwent a brief burst (<1 hour) of rapid phagocytosis, which was then invariably followed by a sharp reduction in phagocytic activity that could persist for days.
View Article and Find Full Text PDFPhagocytosis is a dynamic process central to immunity and tissue homeostasis. Current methods for quantification of phagocytosis largely rely on indirect or static measurements, such as target clearance or dye uptake, and thus provide limited information about engulfment rates or target processing. Improved kinetic measurements of phagocytosis could provide useful, basic insights in many areas.
View Article and Find Full Text PDFCD20 monoclonal antibody therapies have significantly improved the outlook for patients with B-cell malignancies. However, many patients acquire resistance, demonstrating the need for new and improved drugs. We previously demonstrated that the natural process of antibody hexamer formation on targeted cells allows for optimal induction of complement-dependent cytotoxicity.
View Article and Find Full Text PDFCancer Immunol Res
October 2018
CD20 monoclonal antibodies (CD20 mAb) induce cellular cytotoxicity, which is traditionally measured by antibody-dependent cellular cytotoxicity (ADCC) assays. However, data suggest that antibody-dependent cellular phagocytosis (ADCP) is the primary cytotoxic mechanism. We directly compared ADCP versus ADCC using primary human cells.
View Article and Find Full Text PDFWe examined complement-dependent cytotoxicity (CDC) by hexamer formation-enhanced CD20 mAb Hx-7D8 of patient-derived chronic lymphocytic leukemia (CLL) cells that are relatively resistant to CDC. CDC was analyzed in normal human serum (NHS) and serum from an individual genetically deficient for C9. Hx-7D8 was able to kill up to 80% of CLL cells in complete absence of C9.
View Article and Find Full Text PDFPurpose: Tear cytokines and matrix metalloproteinases (MMPs) can be extracted from the Schirmer strip. This study examined the extracted levels of tear cytokines and MMPs from Schirmer strips and potential correlation with Schirmer's test, tear breakup time (TBUT), tear osmolarity, and ocular surface disease index (OSDI).
Methods: Thirty healthy volunteers were clinically evaluated for known methods to diagnose dry eye disease, including Schirmer's test, tear osmolarity, OSDI, and TBUT.
Purpose: The Schirmer's test is commonly used in the clinic for the diagnosis of dry eye disease by measuring tear volume. This report describes a procedure which can be used to recover tears from the Schirmer strip for the measurement of multiple tear cytokines as well as matrix metalloproteinases (MMPs) by Luminex technology.
Methods: Cytokine and MMP recovery was determined by using spiked Schirmer strips presoaked with known cytokines or MMPs prepared in PBS with 1% BSA.
Purpose: BOL-303242-X is a novel selective glucocorticoid receptor agonist under clinical evaluation for the treatment of inflammatory skin and eye diseases. Data from in vitro and in vivo studies suggest an improved side-effect profile of this compound compared to classical glucocorticoids. The aim of this study was to determine the anti-inflammatory effect of BOL-303242-X in ocular cells.
View Article and Find Full Text PDFPurpose: To determine the effect of four marketed multipurpose contact lens solutions (MPSs) on corneal epithelial cell viability.
Methods: Comparison of the effect of MPS A (Renu MultiPlus, Bausch & Lomb), MPS B (OPTI-FREE Express, Alcon), MPS C (AQuify, CibaVision), and MPS D (OPTI-FREE RepleniSH, Alcon) on cell viability was performed by quantifying cellular ATP content, resazurin reduction, and lactate dehydrogenase (LDH) release in transformed human corneal epithelial cells (HCEpiC) and primary bovine corneal epithelial cells (BCEpiC).
Results: Significant reductions in cellular ATP content were observed at 40% solution and above with both MPS B and MPS D, compared to at 100% only for MPS A and MPS C, and similar results were obtained in BCEpiC.