Alteration in the gene expression pattern of primary monocytes after adhesion to endothelial cells

Abstract

Monocytes originate from precursors made in the bone and remain in the circulation for nearly 24 h. Much effort has been done to identify the molecules regulating transendothelial migration of monocytes during inflammatory conditions. In contrast, considerably less is known about the process of constitutive monocyte emigration although nearly 340 million monocytes leave the circulation each day in healthy individuals. Previous studies indicated that chemokines were up-regulated in monocytes cocultured with endothelial cells that induce the retraction of the latter cell type, thereby increasing vascular permeability. Thus, we hypothesized that the utilities required for efficient constitutive monocyte extravasation are generated by monocytes themselves because of adhesion to naïve endothelial cells. To test this hypothesis, cDNA microarray analysis was performed to determine the changes in the gene expression pattern of primary monocytes that have been attached to endothelial cells compared with monocytes that were held in suspension, and we were able to identify three major groups of genes. The first group includes genes such as matrix metalloproteinase 1, monocyte chemoattractant protein 1, and tissue transglutaminase 2, which are likely required for monocyte extravasation. The second group consists of genes that are expressed in phagocytes such as caveolin-1 and CD74. Finally, the third group comprises genes that are expressed in cells of endothelial tissue and cartilage including E-selectin, fibronectin-1, matrix Gla protein, and aggrecanase-2. In summary, we conclude that adhesion of peripheral blood monocytes to naïve endothelial cells has two effects: mandatory extravasation-specific genes are regulated, and the differentiation program of monocytes is initiated. differentiation ͉ cDNA microarray

Kainic acid induces expression of caveolin-1 in activated microglia in rat brain

“…Although the expression of caveolin-1 in immune cells has long been debated [14], a body of evidence indicates that macrophages actually express caveolin-1 in pathological conditions [15]. In addition, it is reported that the expression of caveolin-1 gene is up-regulated in monocytes after activation by adhesion to endothelial cells [16]. The present study provides additional evidence indicating that caveolin-1 plays roles in tissue injuries through cells of the mononuclear phagocytic system.…”

“…Total RNA was extracted from fresh tissues of right cerebral cortex and hippocampus using the acid guanidium thiocyanate-phenol method. Five mg of each total RNA was reversely transcribed for the synthesis of the first strand cDNA using 500 pmol of oligodT [12][13][14][15][16][17][18] (Amersham Biosciences Corp., Arlington Heights, IL) and 200 units of SuperScript II (Gibco BRL, Gaithersburg, MD).…”

Transglutaminases in Vascular Biology: Relevance for Vascular Remodeling and Atherosclerosis

“…These cross-linked receptors display enhanced activity, which is associated with increased adhesion of monocytes to the endothelium and increased symptoms of atherosclerosis in ApoE-deficient mice [40]. Attachment of monocytes to endothelial cells induces an upregulation of type 2 Tgase in monocytes, and is considered to participate in the process of cell adhesion and transmigration [41]. When monocytes are placed into culture and mature into macrophages, a shift from factor XIII expression to type 2 Tgase is noted [42].…”

D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion

“…To test this, and given the difficulties in transfecting and working with LECs in vitro, we used HUVECs as a model of inflammatory leukocyte binding to endothelial cells. 40 In this model, HUVECs are treated with TNF to induce inflammatory CC-chemokines (including CCL2), selectins, and intergrins. These are presented on the HUVEC surface allowing attachment of THP-1 or other inflammatory chemokine receptor-bearing cells.…”