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C-type lectins, a superfamily of type II transmembrane proteins, are calcium-dependent carbohydrate-recognition proteins that bind to a diverse array of glycoconjugates. However, their ligand specificities are poorly understood and roles for lectins in immunity and cancer are only recently becoming elucidated. In this study, we identified CARMIL-2, an endoplasmic reticulum (ER)-resident lectin, as a novel hematopoietic C-type lectin that binds sialic acid and is expressed on human myeloid cells. CARMIL-2 has a structural motif that is conserved in other known lectins, which suggests that it functions as a lectin, but the biochemical properties of CARMIL-2 differ from other lectins. Genetic and biochemical analysis of CARMIL-2 demonstrates that it plays a role in glucose homeostasis and hematopoietic stem cell function. Overexpression of CARMIL-2 in transgenic mice leads to a reduction in the number of hematopoietic stem cells. We have also found that CARMIL-2 knockout mice display increased survival and a longer lifespan under normal conditions. These findings indicate that CARMIL-2 can be a target for future anti-cancer treatments. Further, we have characterized the ligand specificity of CARMIL-2 by mass spectrometry, resulting in the identification of a new ligand for CARMIL-2 and a biological function for CARMIL-2 in mediating hematopoietic stem cell self-renewal.
While investigating the association between prostatic inflammation and prostate cancer, we have observed a surprising association between the appearance of CD4+ T cells in the peripheral blood and the presence of semen in the prostate. We have confirmed this association in two independent patient populations. We have also confirmed that CD4+ T cells are present in ejaculate and thought to be important in the process of fertilization. We hypothesize that semen is a key player in this process and that the semen-associated CD4+ T cells are involved. Alternatively, CD4+ T cells may be induced to appear in the blood as a consequence of semen exposure. Based on our observations, we suggest that the presence of semen during prostatic inflammation may be a key factor in the development of prostatic inflammation in some patients with cancer. Specifically, we suggest that semen may be a key factor in the induction of peripheral T cell blood lymphocytosis in some patients with cancer of the prostate.
Background: The transient receptor potential vanilloid subtype 1 (TRPV1) is a unique protein channel predominantly located in sensory neurons. TRPV1 plays a key role in the detection of a noxious heat and is also involved in the regulation of body temperature.
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