Study on integrin-mediated albumin microbubbles adherence to activated leukocytes

AIM:To investigate the mechanism responsible for albumin microbubbles adherence to activated leukocytes. METHODS: In vitro studies were performed in which activated or nonactivated leukocytes were incubated with albumin microbubbles and observed under microscopy. The suspensions of leukocytes and microbubbles which contained or absented of integrins were analyzed with flow cytometry.RESULTS: A minimum of 50cells were identified under transillumination. 5 min after microbubbles were incubated with leukocytes, the number of cells interacting with microbubbles was greater for activated cells than for nonactivated cells(20.30±2.67 vs 4.50±1.43, P <0.01).Microbubbles attached to the surface of activated leukocytes were phagocytosed and remained intact for up to 30min. Microbubble attachment was inhibited notably by blocking the leukocyte β₂-integrin Mac-1(P <0.01) and by VLA-4mAb slightly(P <0.05) CONCLUSION: The mechanism of albumin microbubbles attaching to and phagocytosed by leukocytes was due to β₂-integrin and VLA-4 mediation. Phagocytosed microbubbles can remain at the regions of inflammation for15 min, also responsible to ultrasound.     

Integrins and cardiovascular diseases

The adhesion of cells to each other and to the proteins of the extracellular matrix provides a stable environment for cell growth, differentiation and migration. This is a prerequisite for the normal function of the cardiovascular system. Thus the abnormal adhesion function may play a key role in the pathogenesis and development of cardiovascular diseases. To date, there are six main groups of adhesion molecule, and integrins family are the largest and most broadly distributed of the families of cellular adhesion receptors. They have an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence andmortality due to these disorders. This review focuses upon the structure, mechanism and their roles in cardiovascular diseases which maybe facilitate the development of novel therapies.     

The sensation and transduction of mechanical stimulus in cells

Mechanical stresses modulate almost all aspects of cell function, including growth, differentiation, migration, gene expression, protein synthesis and apoptosis. Thus, uncovering the mechanisms by which living cells sense and transduce mechanical stress lies at the core of understanding how they respond and adapt to their physical environments. In this review, the possible mechanism about cell response to mechanical stimulus was discussed from outer cell membrane to inner nucleus.     

Cell adhesion molecules, leukocyte trafficking, and strategies to reduce leukocyte infiltration

Leukocyte-endothelial cell interactions are mediated by various cell adhesion molecules. These interactions are important for leukocyte extravasation and trafficking in all domestic animal species. An initial slowing of leukocytes on the vascular endothelium is mediated by selectins. This event is followed by (1) activation of beta2 integrins after leukocyte exposure to cytokines and pro-inflammatory mediators, (2) adherence of leukocyte beta2 integrins to vascular endothelial ligands (eg, intercellular adhesion molecule-1 [ICAM-1]), (3) extravasation of leukocytes into tissues through tight junctions of endothelial cells mediated by platelet and endothelial cell adhesion molecule-1 (PECAM-1), and (4) perivascular migration through the extracellular matrix via beta1 integrins. Inhibiting excessive leukocyte egress and subsequent free radical-mediated damage caused by leukocyte components may attenuate or eliminate tissue damage. Several methods have been used to modify leukocyte infiltration in various animal models. These methods include nonspecific inhibition of pro-inflammatory mediators and adhesion molecules by nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, inhibition of cytokines and cytokine receptors, and inhibition of specific types of cell adhesion molecules, with inhibitors such as peptides and antibodies to beta2 integrins, and inhibitors of selectins, ICAMs, and vascular cell adhesion molecule-1 (VCAM-1). By understanding the cellular and molecular events in leukocyte-endothelial cell interactions, therapeutic strategies are being developed in several animal models and diseases in domestic animal species. Such therapies may have clinical benefit in the future to overcome tissue damage induced by excessive leukocyte infiltration.     

整合素LFA-1研究进展

整合素是白细胞表面受体的主要家族,主要介导细胞与细胞外基质间的黏附,调节白细胞的迁移、存活、增殖和血管生成等过程中发挥关键作用。LFA-1作为白细胞整合素的重要成员具有复杂结构和重要生物学功能,该文就其近年研究进展情况做一综述。     

Intracellular signal transduction pathway of integrin and hepatic stellate cell behavior

Integrins are the main mediators of the complicated interaction between hepatic stellate cells (HSCs) and extracellular matrix (ECM) components. Signal transduction by integrins is initiated by both occupancy and crosslinking of integrins by ECM components. Focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK), which are the downstream molecules, involve in integrin-mediated cellular behaviors. In this review, we briefly summarize the integrin's structure, intracellular signaling cascades and its role in HSC behaviors, such as activation, proliferation and apoptosis.     

Effect of bFGF on human kidney fibroblasts

AIM: To study the effect of bFGF on cell proliferation, secretion of type I collagen and expression of integrin β₁ in human kidney fibroblasts(KFB). METHODS: The KFB was cultured and stimulated by bFGF in vitro. The proliferation and collagen I secreting of KFB, the expression of integrin β₁ were measured by MTT, ELISA and flow cytometer, respectively. RESULTS: bFGF(25-50 μg/L) could obviously stimulate the cell proliferation(P< 0.05), promote the secretion of collagen I(P< 0.05) and enhance the expression of integrin β₁(P< 0.05) in human kidney fibroblast. CONCLUSION: bFGF could induce renal interstitial fibrosis by promoting cell proliferation, secretion of collagen I and integrin β₁ expression of KFB.     

Engagement of integrins as a cellular route of invasion by bacterial pathogens

Integrins are heterodimeric receptors that mediate important cell functions, including cell adhesion, migration and tissue organisation. These transmembrane receptors regulate the direct association of cells with each other and with extracellular matrix proteins. However, by binding their ligands, integrins provide a transmembrane link for the bidirectional transmission of mechanical forces and biochemical signals across the plasma membrane. Interestingly, several of this family of receptors are exploited by pathogens to establish contact with the host cells. Hence, microbes subvert normal eukaryotic cell processes to create a specialised niche which allows their survival. This review highlights the fundamental role of integrins in bacterial pathogenesis.     

Effect of bFGF on expression of endothelial cell integrin β1 subunits

AIM: To study the effect of basic fibroblast growth factor(bFGF) to the expression of integrin β₁ subunit of endothelial cells. METHOD: The expression of integrin β₁ subunit of endothelial cells was determined before and after bFGF treatment with Western Blot and immage analysis method.RESULTS: The mean gray value of immunostain by immage analysis method is 166.11±9.86 in the experimental group and 175.32±5.12 in the control group, suggested that bFGF may upregulate expression of integrin β₁ subunits of endothelial cell. CONCLUSION: bFGF may play an important role in angiogenesis by way of inducing the overexpression of endothelial cell integrin β₁ subunits.