Leukocyte integrins and inflammation

Gahmberg, Carl G.; Valmu, Leena; Fagerholm, Susanna C.; Kotovuori, Pekka; Ihanus, Eveliina; Tian, Li; Pessa‐Morikawa, Tiina

doi:10.1007/s000180050183

Cited by 92 publications

(84 citation statements)

References 50 publications

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“…Conversely, CD11b is implicated in various adhesive interactions of myeloid cells (macrophages, monocytes, and granulocytes) (Ji, 2012) and belongs to a family of integrins (Arnaout, 1990). It is found also on natural killer (NK) cells and certain subpopulations of B lymphocytes (Flotte et al 1983;Gahmberg et al, 1998;Liu et al, 2004;Solovjov et al, 2005), but not on dendritic cells. The macrophage population represents the complexity of various phenotypes during embryonic development (Leenen et al, 1994); however, since this marker is often utilized for detection of embryonic macrophages, we can posit that these scattered cells bearing CD11b or/and F4/80 markers of embryonic heart are macrophages.…”

Section: Discussionmentioning

confidence: 99%

Cellular phenotypes and spatio‐temporal patterns of lymphatic vessel development in embryonic mouse hearts

Flaht

Jankowska‐Steifer

Radomska

et al. 2012

Developmental Dynamics

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Di‐stereoblock polylactides (di‐sb‐PLA: PLLA‐b‐PDLA) having high molecular weight (Mn > 100 kDa) were successfully synthesized by two‐step ring‐opening polymerization (ROP) of L‐ and D‐lactides using tin(2‐ethylhexanoate) as a catalyst. By optimizing the polymerization conditions, the block sequences were well regulated at non‐equivalent feed ratios of PLLA and PDLA. This synthetic method consisted of three stages: (1) polymerization of either L‐ or D‐lactide to obtain a PLLA or PDLA prepolymer with a molecular weight less than 50 kDa, (2) purification of the obtained prepolymer to remove residual lactide, and (3) polymerization of the enantiomeric lactide in the presence of the purified prepolymer. Their 13C and 31P NMR spectra of the resultant di‐sb‐PLAs strongly supported their di‐stereo block structure. These di‐sb‐PLAs, having weight‐average molecular weights higher than 150 kDa, were fabricated into polymer films by solution casting and showed exclusive stereocomplexation. The thermomechanical analysis of the films revealed that their heat deformation temperature was limited probably because of their low crystallinity owing to the non‐equivalent PLLA/PDLA ratio. The blend systems of the di‐sb‐PLAs having complementary stereo‐sequences (the one with a long PLLA block and the other with long PDLA block) were also prepared and characterized to enhance the sc crystallinity. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 794–801, 2010

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Section: Discussionmentioning

confidence: 99%

Cellular phenotypes and spatio‐temporal patterns of lymphatic vessel development in embryonic mouse hearts

Flaht

Jankowska‐Steifer

Radomska

et al. 2012

Developmental Dynamics

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“…The pivotal role of these integrins for the immune response is documented by the finding that individuals lacking b2-integrins (leukocyte-adhesion deficiency syndrome I) develop severe, life-threatening, bacterial and fungal infections (reviewed in [8]). Previously, we have shown that the human Thy-1 (CD90) is an activation-associated cell-adhesion molecule, which is involved in the adhesion of neutrophils to activated microvascular EC via the interaction with the b2-leukocyte integrin Mac-1 (CD11b/ CD18) [9,10].…”

Section: Introductionmentioning

confidence: 99%

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

et al. 2008

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Neutrophils are the first cells arriving at sites of acute inflammation. On their way from blood to the site of inflammation, neutrophils have to adhere to endothelial cells (EC), to transverse the basement membrane and subsequently to travel through the interstitial matrix. Recently, we have shown that human Thy-1 is an alternate EC receptor for the leukocyte integrin Mac-1 that contributes to leukocyte recruitment to sites of inflammation, providing a new pathway for adhesion and transmigration of neutrophils. Here, we studied the effect of Thy-1-mediated adhesion on neutrophil functions. Binding of neutrophils to recombinant human Thy-1 stimulated the release of MMP-9 from neutrophils, resulting in their enhanced migration through collagen-IV and matrigel. Further, we showed that neutrophil interaction with Thy-1 stimulated secretion of CXCL8 and thus could support the attraction of additional neutrophils to inflammatory sites. Blocking experiments confirmed the pivotal roles of Thy-1 on activated dermal EC or fibroblasts and its counter receptor CD18 on neutrophils for the regulation of MMP-9 and CXCL8 release from neutrophils. Our results support the general concept that the function of 'adhesion molecules' in particular of human Thy-1, may not only be to provide mechanical support but also regulate neutrophil functions.

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“…The integrin LFA-1 (lymphocyte function-associated antigen-1, also known as CD11a/CD18 or ␣ L ␤ 2 ) is a member of the leukocyte (␤2) subfamily of integrins that is expressed on the cell surface of all leukocytes (4,5). This molecule mediates important adhesive phenomena through interactions with its ligands intercellular adhesion molecules (ICAM-1, 1 -2, or -3).…”

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confidence: 99%

Signaling through the Leukocyte Integrin LFA-1 in T Cells Induces a Transient Activation of Rac-1 That Is Regulated by Vav and PI3K/Akt-1

Sánchez-Martı́n

Sánchez-Sánchez

Gutiérrez-López

et al. 2004

Journal of Biological Chemistry

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Integrin LFA-1 is a receptor that is able to transmit multiple intracellular signals in leukocytes. Herein we show that LFA-1 induces a potent and transient increase in the activity of the small GTPase Rac-1 in T cells. Maximal Rac-1 activity peaked 10 -15 min after LFA-1 stimulation and rapidly declined to basal levels at longer times. We have identified Vav, a guanine nucleotide exchange factor for Rac-1, and PI3K/Akt, as regulators of the activation and inactivation phases of the activity of Rac-1, respectively, in the context of LFA-1 signaling based on the following experimental evidence: (i) LFA-1 induced activation of Vav and PI3K/Akt with kinetics consistent with a regulatory role for these molecules on Rac-1, (ii) overexpression of a constitutively active Vav mutant induces activation of Rac independently of LFA-1 stimulation whereas overexpression of a dominant-negative Vav mutant blocks LFA-1-mediated Rac activation, (iii) pharmacological inhibition of PI3K/Akt prevented the fall in the activity of Rac-1 after its initial activation but had no effect on Vav activity, and (iv) overexpression of a dominant-negative or a constitutively active Akt-1 induced or inhibited, respectively, Rac-1 activity. Finally, we show that T cells with a sustained Rac activity have impaired capacity to elongate onto ICAM-1. These results demonstrate that down-regulation of the activity of this GTPase is a requirement for the regulation of T cell morphology and motility and highlight the importance of temporal regulation of the signaling triggered from this integrin.

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Leukocyte integrins and inflammation

Cited by 92 publications

References 50 publications

Cellular phenotypes and spatio‐temporal patterns of lymphatic vessel development in embryonic mouse hearts

Cellular phenotypes and spatio‐temporal patterns of lymphatic vessel development in embryonic mouse hearts

Human Thy‐1 induces secretion of matrix metalloproteinase‐9 and CXCL8 from human neutrophils

Signaling through the Leukocyte Integrin LFA-1 in T Cells Induces a Transient Activation of Rac-1 That Is Regulated by Vav and PI3K/Akt-1

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