Cyclophilin A cooperates with MIP-2 to augment neutrophil migration

Abstract

BackgroundChemokines contribute to inflammatory responses by inducing leukocyte migration and extravasation. In addition, chemoattractants other than classical chemokines can also be present. Many chemokines have been demonstrated to cooperate, leading to an augmentation in leukocyte recruitment and providing a potential role for the presence of multiple chemoattractants. Extracellular cyclophilins are a group of alternative chemotactic factors, which can be highly elevated during various inflammatory responses and, as we have previously shown, can contribute significantly to neutrophil recruitment in an animal model of acute lung inflammation. In the current studies we investigated whether the most abundant extracellular cyclophilin, CypA, has the capacity to function in partnership with 2 classical chemokines known to be secreted in the same model, macrophage inflammatory protein (MIP)-2/CXCL2 and keratinocyte chemoattractant (KC)/CXCL1.MethodsNeutrophil migration in response to combinations of CypA and MIP-2 or CypA and KC was measured by in vitro chemotaxis assays. Biochemical responses of neutrophils incubated with the combinations of chemoattractants were determined by changes in chemokine receptor internalization and actin polymerization measured by flow cytometry, and changes in intracellular calcium mobilization measured with a calcium sensitive fluorochrome.ResultsA combination of CypA and MIP-2, but not KC, augmented neutrophil migration. Based on the level of augmentation, the cooperation between CypA and MIP-2 appeared to be synergistic. Evidence that CypA and MIP-2 cooperate at the biochemical level was demonstrated by increases in receptor internalization, calcium mobilization, and actin polymerization.ConclusionThese findings provide evidence for the capacity of extracellular cyclophilins to interact with classical chemokines, resulting in greater and more efficient leukocyte recruitment.

Side-by-Side Comparison of the Biological Characteristics of Human Umbilical Cord and Adipose Tissue-Derived Mesenchymal Stem Cells

“…The content of some cytokines varied greatly; for example, the expressions of MIP-2, IL-6, and GRO in UC-MSC-CM were significantly higher than those in ASC-CM, while the expressions of CD27 and neuregulin in ASC-CM were significantly higher than those in UC-MSC-CM. MIP-2 is the main chemotactic cytokine of neutrophil, and it can specifically promote neutrophil migrating to the inflammatory tissue, to get rid of pathogens and participate in the body's defense reaction [35]; MMP-1 is involved in mediation of a wide range of physiological and pathological processes in the body, such as the formation of embryo, tissue remodeling, wound healing, inflammation, and apoptosis [36]. IL-6 can promote the proliferation of a variety of cells, and this might be one of the reasons for UC-MSCs proliferating faster than ASCs [37].…”

Cyclophilin A Is Required for Angiotensin II–Induced p47phox Translocation to Caveolae in Vascular Smooth Muscle Cells

“…Most importantly, CyPA has been shown to be a cell cytoskeleton binding protein 19, 20 by which it can regulate neutrophil migration 21 and tumorogenesis 22 through regulating actin polymerization. The role of intracellular CyPA in AngII-induced ROS production in VSMC is still unknown.…”

Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma

“…Macrophage inflammatory protein 2 (MIP-2), the mouse analogue of the human pro-inflammatory cytokine IL-8, is a potent neutrophil chemoattractant. Together with CypA, MIP-2 was demonstrated to have a synergistic effect on neutrophil migration [ 27 ]. In humans, CypA induces the secretion of the pro-inflammatory cytokine IL-8.…”