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Kelly McNagny

Publications and source records attributed to Kelly McNagny.

4 recordsLinked to original sources

Beyond mere markers: functions for CD34 family of sialomucins in hematopoiesis.

CD34, podocalyxin, and endoglycan are members of a family of single-pass transmembrane proteins that show distinct expression on early hematopoietic precursors and vascular-associated tissue. In spite of the fact that the expression of CD34 on these early progenitors has been known for over 20 yr and used clinically in hematopoietic stem cell transplantation for more than 15 yr, little is known about its exact role or function. More recently, CD34 expression has been shown to distinguish activated early progenitors from quiescent cells. With the subsequent identification of podocalyxin and endoglycan as related family members also expressed on early progenitor cells, attention is slowly shifting toward understanding how these molecules might contribute to progenitor function and behavior. In this review we examine the existing evidence and propose testable models to reveal the importance of these molecules for stem and progenitor cell function.

Animals↗

Platelets express functional Toll-like receptor-4.

Profound thrombocytopenia occurs in humans with sepsis and in mice administered lipopolysaccharide (LPS). Growing evidence indicates that platelets may contribute to these abnormalities, but whether that is a direct result of LPS activation of platelets or an indirect result of other inflammatory mechanisms remains unclear. Here we demonstrate that although platelets do not increase P-selectin expression in response to LPS, platelets bind more avidly to fibrinogen under flow conditions in a Toll-like receptor-4 (TLR4)-dependent manner. In addition, we find that CD41+ megakaryocytes grown from fetal livers and adult circulating platelets express significant amounts of TLR4. LPS induced thrombocytopenia in wild-type mice but not in TLR4-deficient (TLR4def) mice. Wild-type platelets accumulated in the lungs of wild-type mice in response to LPS; TLR4def platelets did not. However, wild-type platelets did not accumulate in the lungs of LPS-treated TLR4def mice. Neutrophils also accumulated in the lungs, and this preceded platelet accumulation. Neutrophil depletion completely abolished LPS-induced platelet sequestration into the lungs, but platelet depletion did not affect neutrophil accumulation. Thus, our data show for the first time that platelets do express functional levels of TLR4, which contribute to thrombocytopenia through neutrophil-dependent pulmonary sequestration in response to LPS.

Animals↗

Pattern of expression of the podocalyxin gene in the mouse brain during development.

We studied the expression pattern of the major renal protein Podocalyxin during the development of mouse brain using in situ hybridization. Podocalyxin mRNA was widely expressed at least from E14, the first age we studied, and expression remained high until adulthood. The highest levels of expression were postnatal. Podocalyxin expression was particularly elevated in the cortical plate, the hippocampus and cerebellum, and in several basal forebrain nuclei.

Animals↗