Monocyte Migration and LFA-1-Mediated Attachment to Brain Microvascular Endothelia Is Regulated by SDF-1α through Lyn Kinase

Malik, Mobeen; Chen, Yingyu; Kienzle, Martha; Tomkowicz, Brian; Collman, Ronald G.; Ptasznik, Andrzej

doi:10.4049/jimmunol.181.7.4632

Cited by 43 publications

(35 citation statements)

References 38 publications

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“…However, CXCL12 and CXCL14 were both down-regulated by >2-fold. CXCL12 stimulates the migration of T-lymphocytes, monocytes and neutrophils [47], [48]. CXCL14 (BRAK) is a chemoattractant for macrophages, immature dendritic cells and natural killer cells [49].…”

Section: Discussionmentioning

confidence: 99%

Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

2013

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The ectoparasitic mite, Sarcoptes scabiei that burrows in the epidermis of mammalian skin has a long co-evolution with its hosts. Phenotypic studies show that the mites have the ability to modulate cytokine secretion and expression of cell adhesion molecules in cells of the skin and other cells of the innate and adaptive immune systems that may assist the mites to survive in the skin. The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents (HSEs) that changed expression in response to the burrowing of live scabies mites. Overall, of the more than 25,800 genes measured, 189 genes were up-regulated >2-fold in response to scabies mite burrowing while 152 genes were down-regulated to the same degree. HSEs differentially expressed large numbers of genes that were related to host protective responses including those involved in immune response, defense response, cytokine activity, taxis, response to other organisms, and cell adhesion. Genes for the expression of interleukin-1α (IL-1α) precursor, IL-1β, granulocyte/macrophage-colony stimulating factor (GM-CSF) precursor, and G-CSF precursor were up-regulated 2.8- to 7.4-fold, paralleling cytokine secretion profiles. A large number of genes involved in epithelium development and keratinization were also differentially expressed in response to live scabies mites. Thus, these skin cells are directly responding as expected in an inflammatory response to products of the mites and the disruption of the skin’s protective barrier caused by burrowing. This suggests that in vivo the interplay among these skin cells and other cell types, including Langerhans cells, dendritic cells, lymphocytes and endothelial cells, is responsible for depressing the host’s protective response allowing these mites to survive in the skin.

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Section: Discussionmentioning

confidence: 99%

Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

2013

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“…We, and others, have previously shown that Lyn kinase is involved in chemoattractant signaling (Ptasznik et al, 1995, 1996; Mócsai et al, 2000) and is required for CXCR4-mediated chemotaxis of hematopoietic cells and macrophages (Ptasznik et al, 2002; Malik et al, 2008; Tabe et al, 2012). Here we provide results indicating that Lyn is also required for CXCR4-mediated migration of stellate cells in inflamed pancreas.…”

Section: Introductionmentioning

confidence: 96%

Essential Role of Lyn in Fibrosis

et al. 2016

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Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation, and collagen production, is a key target for preventing fibrosis.

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“…26 Stromal derived factor-1 (SDF-1) is an important chemokine that is detectable in primary atherosclerotic plaques. 1 Studies have shown that SDF-1 was involved in the cellular adhesion mediated by intercellular adhesion molecule 1 (ICAM-1) and cooperated with ICAM-1 to capture progenitor cells from blood and to induce transendothelial migration of monocytes, 17 suggesting a critical role of SDF-1 in the mechanism of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of SDF-1 is Associated with Atherosclerosis Lesions Induced by LDL Concentration Polarization

et al. 2012

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Previous numerical simulations on low-density lipoprotein (LDL) concentration polarization in the arterial system indicated that LDL concentration polarization might play an important role in the genesis and development of atherosclerosis. To date, no in vivo experiments have examined this question directly, and the molecular mechanisms are unknown. In this study, ten rabbits were treated with gel-silica loop to develop a defined local stenosis in the straight segment of the left carotid artery. Both numerical simulation and experiment measurements showed that the concentration of LDL was about 35% higher at the blood/arterial wall interface than in the lumen on the distal side of the stenosis. Atherosclerotic lesions with abundant lipid deposits were observed and stromal derived factor-1 (SDF-1) was detected at the distal end of the stenosis, while the straight segment was plaque-free. In vitro studies demonstrated that LDL-induced SDF-1 expression in endothelial cells and increased monocyte adhesion to endothelial cells in a dose-dependent manner. The adhesion was suppressed when endothelial cells were pretreated with SDF-1 antibody. These results suggested LDL concentration polarization contributed to the localization of atherosclerosis and to the expression of SDF-1. In turn, SDF-1 facilitated plaque formation.

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Monocyte Migration and LFA-1-Mediated Attachment to Brain Microvascular Endothelia Is Regulated by SDF-1α through Lyn Kinase

Cited by 43 publications

References 38 publications

Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

Essential Role of Lyn in Fibrosis

Upregulation of SDF-1 is Associated with Atherosclerosis Lesions Induced by LDL Concentration Polarization

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