It binds gram-negative bacteria and is overexpressed in cancers, where it is antiapoptotic and promotes metastases. To characterize CEACAM6 expression in developing lung, we cultured human fetal lung epithelial cells and examined responses to differentiation-promoting hormones, adenovirus expressing thyroid transcription factor-1 (TTF-1), and silencing of TTF-1 with small inhibitory RNA. Glucocorticoid and cAMP had additive stimulatory effects on CEACAM6 content, and combined treatment maximally increased transcription rate, mRNA, and protein ϳ10-fold. Knockdown of TTF-1 reduced hormone induction of CEACAM6 by 80%, and expression of recombinant TTF-1 increased CEACAM6 in a dosedependent fashion. CEACAM6 content of lung tissue increased during the third trimester and postnatally. By immunostaining, CEACAM6 was present in fetal type II cells, but not mesenchymal cells, and localized to both the plasma membrane and within surfactant-containing lamellar bodies. CEACAM6 was secreted from cultured type II cells and was present in both surfactant and supernatant fractions of infant tracheal aspirates. In functional studies, CEACAM6 reduced inhibition of surfactant surface properties by proteins in vitro and blocked apoptosis of electroporated cultured cells. We conclude that CEACAM6 in fetal lung epithelial cells is developmentally and hormonally regulated and a target protein for TTF-1. Because CEACAM6 acts as an antiapoptotic factor and stabilizes surfactant function, in addition to a putative role in innate defense against bacteria, we propose that it is a multifunctional alveolar protein.alveolar type II cells; thyroid transcription factor-1; glucocorticoid; adenosine 3Ј,5Ј-cyclic monophosphate; apoptosis; surfactant THE IGCAM SUPERFAMILY is a diverse group of adhesive receptor glycoproteins that contain an amino-terminal N domain, which is homologous to the Ig variable domain, and different numbers of domains homologous to the Ig constant domain. In the human, the carcinoembryonic antigen (CEA) gene family is an IgCAM subset consisting of 29 related genes and pseudogenes clustered at q13.2 on chromosome 19 (22). CEA proteins function as intercellular homophilic and heterophilic adhesion molecules and have signaling properties.Carcinoembryonic cell adhesion molecule (CEACAM)6 (also called NCA, NCA-50/90, and CD66c) and CEACAM5 (originally called CEA and also designated CD66e) share ϳ90% homology of the N domain but differ in the number of IgC2-like domains (A and B domains). Both proteins contain a glycosylphosphatidylinositol (GPI) membrane anchor (28) and are targeted to lipid rafts in apical membranes of polarized epithelial cells (32). CEACAM5/6 bind a variety of gramnegative bacteria and mediate internalization/phagocytosis, participating in innate immune defense in the intestine (10). The two genes are not found in rodents, and they may represent pathogen-host coevolution, providing different protein structures with selective bacterial binding properties.Expression of CEACAM5/6 is deregulated and overexpresse...

PL. Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung. Am J Physiol Lung Cell Mol Physiol 302: L216 -L225, 2012. First published October 28, 2011 doi:10.1152/ajplung.00055.2011.-Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycophosphatidylinositol-anchored protein expressed in epithelial cells of various primate tissues. It binds gram-negative bacteria and is overexpressed in human cancers. CEACAM6 is associated with lamellar bodies of cultured type II cells of human fetal lung and protects surfactant function in vitro. In this study, we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature infants at birth and increased progressively in intubated infants with lung disease. Of surfactant-associated CEACAM6, ϳ80% was the fully glycosylated, 90-kDa form that contains the glycophosphatidylinositol anchor, and the concentration (3.9% of phospholipid for adult lung) was comparable to that for surfactant proteins (SP)-A/B/C. We examined the affinity of CEACAM6 by purification of surfactant on density gradient centrifugation; concentrations of CEACAM6 and SP-B per phospholipid were unchanged, whereas levels of total protein and SP-A decreased by 60%. CEACAM6 mRNA content decreased progressively from upper trachea to peripheral fetal lung, whereas protein levels were similar in all regions of adult lung, suggesting proximal-to-distal developmental expression in lung epithelium. In adult lung, most type I cells and ϳ50% of type II cells were immunopositive. We conclude that CEACAM6 is expressed by alveolar and airway epithelial cells of human lung and is secreted into lung-lining fluid, where fully glycosylated protein binds to surfactant. Production appears to be upregulated during neonatal lung disease, perhaps related to roles of CEACAM6 in surfactant function, cell proliferation, and innate immune defense. alveolar type II cells; lung lining fluid; surfactant; airway epithelium CARCINOEMBRYONIC CELL ADHESION molecule 6 (CEACAM6) (also called NCA, NCA-50/90, and CD66c) is a member of the carcinoembryonic antigen (CEA) gene family, consisting of 29 related genes. CEA proteins function as intercellular homophilic and heterophilic adhesion molecules and have signaling properties (18). CEACAM6 contains a glycophosphatidylinositol (GPI) membrane anchor (23) and is targeted to lipid rafts in apical membranes of polarized epithelial cells (26). CEACAM6 binds a variety of gram-negative bacteria and mediates internalization and phagocytosis, participating in innate immune defense in the intestine (13). The CEACAM6 gene is not present in rodents, and its emergence in primates may represent pathogen-host coevolution, providing different protein structures with selective bacterial binding properties.Expression of CEACAM6 and closely related CEACAM5 is deregulated and overexpressed in cancers of colorectal epithelium, with surface levels inversely correlated with both the degree of colonocyte differentiat...

acidosis (EA) has profound effects on vascular homeostasis, including vascular bed-specific alterations in vascular tone. Regulation of gene expression by EA has been observed in a variety of cells including vascular endothelial cells. Whether EA regulates gene expression in vascular smooth muscle cells (VSMCs) is not known. Heme oxygenase (HO)-1 is expressed in vascular cells, and its expression is regulated by cellular stressors such as heat, radiation, and hypoxia. Increased HO-1 expression in VSMCs leads to increased production of CO and its second messenger cGMP, which are important regulators of vascular tone and paracrine interactions in the vasculature. We examined whether EA regulates the expression of HO-1 in VSMCs. Exposure of VSMCs to acidic medium (pH 6.8) significantly increased HO-1 mRNA and protein compared with exposure to medium of physiological pH (pH 7.4). The acidic induction of HO-1 expression was time dependent and involved both transcriptional activation of the HO-1 gene and enhanced stability of HO-1 mRNA. Nitric oxide did not appear to mediate this response. We conclude that HO-1 is transcriptionally and posttranscriptionally upregulated by EA in VSMCs. This induction is time dependent and reversible. We speculate that EA, as an important tissue and cellular stressor for VSMCs, may elicit changes in gene expression patterns that contribute to the maintenance or disruption of vascular homeostasis. transcriptional activation; ribonucleic acid stabilization EXTRACELLULAR ACIDOSIS (EA) is a common clinical state that has profound cardiovascular effects. Although extracellular pH is normally maintained within narrow limits around 7.4, a number of acute and chronic disorders disrupt the acid-base homeostatic mechanisms and lead to systemic acidemia. In addition, local tissue acidosis is found in areas of inflammation, ischemia, and/or hypoxia as well as within solid tumors (36). Systemic acidemia leads to vascular bed-specific alterations in vascular tone and modulation of cardiac contractility. Local tissue acidosis is an important modulator of tumor invasiveness (20) and susceptibility of tumors to radiation, chemotherapy (20), and antiangiogenic therapy (34). The cellular and molecular events mediating the effects of acidosis on vascular homeostasis are incompletely understood. Because acidosis often coexists with hypoxia, the role of acidosis as an independent modulator of vascular cell behavior has, until recently, been overlooked. However, recent studies in vitro and in vivo support the idea that EA has cellular effects independent of hypoxia (2,9,21,27,32,35).Heme oxygenase (HO) and its enzymatic products biliverdin and CO have received increasing recognition as biologically important modulators of cellular interactions in the vasculature. The inducible form of this enzyme, HO-1, is ubiquitously distributed in mammalian tissues, and its expression is regulated by a number of nonheme inducers such as cytokines, heavy metals, hormones and endotoxin (1). In addition, a number of cellular ...

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In studying a collection of Tingidac from the New Haven Connecticut Agricultural Experiment Station, two somewhat damaged specimens of an unfamiliar Stephanitis were noted. Since no description of the species could be found in the literature dealing with American .species, they were sent to Dr. Reece I. Sailer for determination. They proved to be Stephanits globulifera (Matsumura) when compared with specimens in the .National Museum. The species was first described by Matsumura as Tingis globulifera in 1905. Later Horvth (1912) properly transferred it to the genus Stephanitis and redescribed it in some detail. In a 1930 publication Matsumura supplied an English translation of the description which is not very satisfactory and a very small, unsatisfactory figure is also given. Since these three references are not generally available,

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