Annexin A2 antibodies but not inhibitors of the annexin A2 heterotetramer impair productive HIV-1 infection of macrophages in vitro

During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the interaction between A2 and S100A10 were tested for their ability to impair productive HIV-1 infection of macrophages. Our data suggest that interactions between HIV-1 gp120 and A2 exist, though this interaction may be indirect. Furthermore, an anti-A2 antibody impaired HIV-1 particle production in macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote HIV-1 infection of macrophages in its monomeric rather than tetrameric form

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin, but not epidermal Langerhans cells, are depleted by treatment with cyclosporin A

Since cyclosporin A (CsA) is an immuno-suppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3,7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1 + (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1 + DR + cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1 + DR + ), were also reduced after CsA, epidermal non-Langerhans CD1 - DR + cells (macrophages, activated T cells, DR - keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1 + DR + Langerhans cells/non-Langerhans CD1 - DR + epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14. Thus, early in the course of therapy, CsA appears to be effective at clearing CD1 - DR + cells while leaving LC relatively intact in the epidermis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47242/1/403_2004_Article_BF00431054.pd

Reciprocal Prospective Relationships Between Loneliness and Weight Status in Late Childhood and Early Adolescence

Adolescents who do not conform to weight ideals are vulnerable to disapproval and victimization from peers in school. But, missing from the literature is a prospective examination of weight status and feelings of loneliness that might come from those experiences. Using data from the Québec Longitudinal Study of Child Development, we filled that gap by examining the prospective associations between loneliness and weight status when the sample was aged 10 to 13 years. At ages 10, 12, and 13 years, 1042 youth (572 females; 92% from French speaking homes) reported on their loneliness and were weighed and measured. Family income sufficiency was included in our analyses given its relationship with weight status, but also its possible link with loneliness during early adolescence. The findings showed that (1) weight status and loneliness were not associated concurrently; (2) weight status predicted increases in loneliness from ages 12 to 13 years; and (3) loneliness predicted increases in weight from ages 12 to 13 years among female adolescents, but weight loss among male adolescents. The fact that loneliness was involved in weight gain for females suggests that interventions focused on reducing loneliness and increasing connection with peers during early adolescence could help in reducing obesity