EFFECT OF HABITAT AND FORAGING HEIGHT ON BAT ACTIVITY IN THE COASTAL PLAIN OF SOUTH CAROLINA

Double-crested cormorant (Phalacrocorax auritus) populations on the Great Lakes expanded greatly during the past 2 decades. On Lake Erie, the number of breeding cormorants increased from 174 birds (87 nests) in 1979 to 26,542 (13,271 nests) in 2000. In 2000, 81% of the breeding population was on 2 western-basin islands (East Sister and Middle Islands). The plant communities on these islands represent some of the last remnants of Carolinian vegetation in Canada. Our study is the first to quantitatively assess the relationship between the distribution of nesting cormorants and forest health. On East Sister Island, 2 measures of forest cover were obtained using infrared aerial photographs and ground-based measurements of leaf area index. These measures of forest cover were correlated (rs = 0.70, P < 0.001), which validated the use of remotely sensed data to assess forest cover. Cormorant nest density was negatively correlated with tree cover on both East Sister and Middle Islands. Temporal comparisons of Middle Island data indicated a reduction in tree cover from 1995 to 2001, and these reductions coincided with a large increase in the island's cormorant population. Although correlational in nature, our results suggest that cormorants may be detrimentally affecting island forests

Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response

Hem-1 Complexes Are Essential for Rac Activation, Actin Polymerization, and Myosin Regulation during Neutrophil Chemotaxis

Migrating cells need to make different actin assemblies at the cell's leading and trailing edges and to maintain physical separation of signals for these assemblies. This asymmetric control of activities represents one important form of cell polarity. There are significant gaps in our understanding of the components involved in generating and maintaining polarity during chemotaxis. Here we characterize a family of complexes (which we term leading edge complexes), scaffolded by hematopoietic protein 1 (Hem-1), that organize the neutrophil's leading edge. The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE)2 complex, which mediates activation of actin polymerization by Rac, is only one member of this family. A subset of these leading edge complexes are biochemically separable from the WAVE2 complex and contain a diverse set of potential polarity-regulating proteins. RNA interference–mediated knockdown of Hem-1–containing complexes in neutrophil-like cells: (a) dramatically impairs attractant-induced actin polymerization, polarity, and chemotaxis; (b) substantially weakens Rac activation and phosphatidylinositol-(3,4,5)-tris-phosphate production, disrupting the (phosphatidylinositol-(3,4,5)-tris-phosphate)/Rac/F-actin–mediated feedback circuit that organizes the leading edge; and (c) prevents exclusion of activated myosin from the leading edge, perhaps by misregulating leading edge complexes that contain inhibitors of the Rho-actomyosin pathway. Taken together, these observations show that versatile Hem-1–containing complexes coordinate diverse regulatory signals at the leading edge of polarized neutrophils, including but not confined to those involving WAVE2-dependent actin polymerization

Impaired Rho GTPase activation abrogates cell polarization and migration in macrophages with defective lipolysis

Infiltration of monocytes and macrophages into the site of inflammation is critical in the progression of inflammatory diseases such as atherosclerosis. Cell migration is dependent on the continuous organization of the actin cytoskeleton, which is regulated by members of the small Rho GTPase family (RhoA, Cdc42, Rac) that are also important for the regulation of signal transduction pathways. We have recently reported on reduced plaque formation in an atherosclerotic mouse model transplanted with bone marrow from adipose triglyceride lipase-deficient (Atgl−/−) mice. Here we provide evidence that defective lipolysis in macrophages lacking ATGL, the major enzyme responsible for triacylglycerol hydrolysis, favors an anti-inflammatory M2-like macrophage phenotype. Our data implicate an as yet unrecognized principle that insufficient lipolysis influences macrophage polarization and actin polymerization, resulting in impaired macrophage migration. Sustained phosphorylation of focal adhesion kinase [due to inactivation of its phosphatase by elevated levels of reactive oxygen species (ROS)] results in defective Cdc42, Rac1 and RhoA activation and in increased and sustained activation of Rac2. Inhibition of ROS production restores the migratory capacity of Atgl−/− macrophages. Since monocyte and macrophage migration are a prerequisite for infiltrating the arterial wall, our results provide a molecular link between lipolysis and the development of atherosclerosis

Regulation of macrophage motility by Irgm1

IRG are a family of IFN-regulated proteins that are critical for resistance to infection. Mouse IRG proteins are divided into GMS and GKS subfamilies, based on a sequence within the G1 GTP-binding motif. The GMS proteins have a particularly profound impact on immunity, as typified by Irgm1, of which absence leads to a complete loss of resistance to a variety of intracellular bacteria and protozoa. The underlying molecular and cellular mechanisms are not clear. Here, we use time-lapse microscopy and cell-tracking analysis to demonstrate that Irgm1 is required for motility of IFN-γ-activated macrophages. The absence of Irgm1 led to decreased actin remodeling at the leading edge of migrating macrophages, as well as decreased Rac activation. Although Irgm1 did not localize to the leading edge of migrating macrophages, it was found to regulate the localization of a GKS IRG protein, Irgb6, which in turn, concentrated on the plasma membrane in the advancing lamellipodia, in close apposition to molecular components that regulate membrane remodeling, including Rac, paxillin, and actin. Thus, Irgm1 likely controls macrophage motility by regulating the positioning of specific GKS IRG proteins to the plasma membrane, which in turn, modulate cytoskeletal remodeling and membrane dynamics

Loss of phosphoinositide 3-kinase γ decreases migration and activation of phagocytes but not T cell activation in antigen-induced arthritis

<p>Abstract</p> <p>Background</p> <p>Phosphoinositide 3-kinase γ (PI3Kγ) has been depicted as a major regulator of inflammatory processes, including leukocyte activation and migration towards several chemokines. This study aims to explore the role of PI3Kγ in the murine model of antigen-induced arthritis (AIA).</p> <p>Methods</p> <p>Development of AIA was investigated in wildtype and PI3Kγ-deficient mice as well as in mice treated with a specific inhibitor of PI3Kγ (AS-605240) in comparison to untreated animals. Inflammatory reactions of leukocytes, including macrophage and T cell activation, and macrophage migration, were studied <it>in vivo </it>and <it>in vitro</it>.</p> <p>Results</p> <p>Genetic deletion or pharmacological inhibition of PI3Kγ induced a marked decrease of clinical symptoms in early AIA, together with a considerably diminished macrophage migration and activation (lower production of NO, IL-1β, IL-6). Also, macrophage and neutrophil infiltration into the knee joint were impaired <it>in vivo</it>. However, T cell functions, measured by cytokine production (TNFα, IFNγ, IL-2, IL-4, IL-5, IL-17) <it>in vitro </it>and DTH reaction <it>in vivo </it>were not altered, and accordingly, disease developed normally at later timepoints</p> <p>Conclusion</p> <p>PI3Kγ specifically affects phagocyte function in the AIA model but has no impact on T cell activation.</p

The p110γ isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites

The role of PI-3K in leukocyte function has been studied extensively. However, the specific role of the p110γ isoform of PI- 3K in CD4 T lymphocyte function has yet to be defined explicitly. In this study, we report that although p110γ does not regulate antigen-dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration. Naïve p110γ−/− CD4 lymphocytes are phenotypically identical to their wild-type (WT) counterparts and do not exhibit any defects in TCR-mediated calcium mobilization or Erk activation. In addition, p110γ-deficient CD4 OT.II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. Interestingly, however, antigen-experienced, p110γ-deficient CD4 OT.II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo. Although antigen-activated, p110γ-deficient CD4 T cells express P-selectin ligand, β2 integrin, β1 integrin, CCR4, CXCR5, and CCR7 comparably with WT cells, they exhibit impaired F-actin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22. These findings suggest that p110γ regulates the migration of antigen-experienced effector CD4 T lymphocytes into inflammatory sites during adaptive immune responses in vivo