A survey of species differences in the duration of capacitation, T, has revealed that they closely correlate with sperm cholesterol/phospholipid mole ratios, R: T = 8R -1 (r2 = 0.97, in which r is Pearson's correlation coefficient). Because uterine cells displayed low relative cholesterol concentrations, spermatozoa evidently experience a negative external cholesterol gradient (positive phospholipid gradient) during capacitation. A decrease in sperm R-value is suggested, therefore, to accompany capacitation. The idea received strong support from a kinetic analysis of capacitation intervals, based on the rate of cholesterol efflux from sperm cells in utero. Lipid-binding serum proteins in uterine fluid are attributed with removing a sterol barrier to the Ca2+-facilitated membrane fusion that initiates the acrosome reaction. Tight cell junctions prevent permeation of the male generative tract by these proteins (capacitation factors). Furthermore, seminal plasma contains a decapacitation factor, identified as a membrane vesicle (cholesterol donor) component ofthis fluid, that reverses capacitation. Initiation of the sperm acrosome reaction among mammals could be the first fusion process found to be physiologically modulated through the membrane bilayer cholesterol level.Cells frequently display an intriguing sense oftime. This is certainly conspicuous during embryogenesis of a complex organism. Even before fertilization, however, mammalian gametes change with time.

No abstract

Plasma membrane isolated from rat sperm cells after incubation in vitro had a significantly lower cholesterol/phospholipid mole ratio when the medium contained serum albumin. Transfer of albumin-bound phospholipids to the membrane can largely account for this effect. The result is broadly consistent with a previously proposed model for albumin-induced destabilization of sperm membrane (capacitation) and its reversal by seminal plasma membrane vesicles. Albumin also decreased sialic acid and, more specifically, ganglioside levels, presumably by promoting release of sperm neuraminidase. Cholesteryl ester comprised up to 0.5 mol/mol of cholesterol in these plasma mem rane preparations. Mammalian sperm cells can express fertilizing capacity after incubation in vitro for an interval of usually a few hours in a chemically defined medium containing serum albumin (1-6). Although the molecular changes underlying transformation to a capacitated state are unclear, albumin specifically facilitates this process (4). Substantial changes in sperm plasma membrane proteins accompany incubation with albumin (7); however, they seem to involve proteolysis after the acrosome reaction. A clue that lipid binding by albumin might be involved in its ability to promote capacitation was provided by the observation that presaturation of the protein with cholesterolt abolished this capability (4). In view of this finding and the discovery that cholesterol-bearing decapitation factor (DF) vesicles from seminal plasma and synthetic vesicles containing the sterol block capacitation in rabbit and rat spermatozoa (8-12), changes in the lipid bilayer of the sperm plasma membrane seem to be necessary for expression of fertilizing capacity.One interpretation of these observations is that albumin decreases the cholesterol/phospholipid (Chol/PL) ratio in the sperm plasma membrane (13). Spectroscopic data reveal that cholesterol restricts the thermal motion of fatty acid chains in a phospholipid bilayer above the gel-to-liquid transition temperature (14-16), and this causes a "condensation effect" and decreases permeability (17). An increase in bilayer microviscosity evidently accounts for the inhibit'ry effect of cholesterol on fusion between plasma membranes of cultured muscle cells (18) and synthetic phospholipid membranes (19). Decreasing the Chol/PL ratio in sperm plasma mqmbrane, therefore, may be anticipated to promote fusion with the outer acrosomal membrane; this intracellular fusion occurring in the acrosome reaction is a precondition for mammalian fertilization (20). A vesicle-induced reversal of this putative change in the plasma membrane Chol/PL ratio might account for the ability of these vesicles to inhibit spermatozoan fertilizing capacity reversibly (11,12).To test this idea, plasma membrane preparations isolated from rat spermatozoa after incubation in vitro were partially characterized with respect to their lipid composition. It was anticipated bovine serum albumin would decrease the Chol/PL ratio in sperm plasma membrane i...

The output of secretions from the airway submucosal glands is regulated by vagal efferent nerves. Stimulation of cough receptors increases mucus output reflexly via the vagus nerves. Adrenergic agonists increase submucosal gland secretions in some species, which indicates that adrenergic receptors are present in these cells. However, evidence for adrenergic nervous pathways to the glands is limited. Irritants and drugs stimulate secretion from epithelial cells by direct effects. There is also evidence that the secretion of epithelial cells can be stimulated by parasympathetic nervous pathways in birds but not in mammals. Active ion transport of Cl- toward the lumen and of Na+ toward the submucosa results in net ion movement toward the airway lumen in unstimulated tracheal epithelia. Drugs and mediators increase the net movement of ions toward the lumen. No agents have yet been found that increase net ion movement toward the submucosa. The link between ion transport and water secretion in airway epithelia, although speculative, seems likely in view of the evidence from other epithelia. Since airway epithelium is a "tight junction" epithelium, modification of the tight junction may alter the transepithelial movement of water and ions. We suggest that the depth and consistency of the periciliary layer of airway secretions determine the ability of the cilia to propel the mucoprotein gel and thereby modify mucociliary transport. To achieve this, secretion of mucus must be controlled separately from the secretion of water. Studies are needed to determine which of the specialized functions of the epithelial cells interact to regulate the clearance of secretions from the airway. Is the sol maintained by secretion and reabsorption of fluid across the epithelium? Does the sol move with the gel by ciliary action or does it remain stationary? Do changes in the epithelial tight junctions influence net water movement and thus indirectly alter the depth of the sol layer? To answer these questions, techniques are needed to study subunits of the airway, including isolated surface cells and submucosal glands; and sensitive methods are required to analyze the very small samples of secretions for glycoprotein and electrolyte content. Intracellular measurements of electrolyte concentrations and electrical potentials may help to elucidate the mechanisms of transepithelial ion and water movement. The control system for the production and removal of respiratory tract secretions may be altered in disease. For instance, chronic stimulation of cough receptors causes reflex secretion and may be the cause of the hyperplasia of submucosal glands and of the abnormal secretions that occur in chronic bronchitis and asthma (50, 58). The abnormally viscid mucus in cystic fibrosis may be due to a defect in Cl- transport, which provides too little water for both the gel and sol layers. These speculations are intended to identify areas for further research, which hopefully will reduce the morbidity and mortality in these common lung diseases.

Information regarding the regulation of monocyte chemoattractant protein-1 (MCP-1) in regression of the corpus luteum (CL) is limited. This study tested the hypothesis that endothelial cells derived from bovine CL are a source of MCP-1, and that proinflammatory cytokines, prostaglandin F2alpha (PGF2alpha), and progesterone regulate MCP-1 expression. Endothelial cells were treated without (Control) or with PGF2alpha (1 micro M), TNFalpha (100 ng/ml), interferon-gamma (IFNgamma, 200 IU/ml), and TNFalpha + IFNgamma for 24 and 48 h in the absence or presence of progesterone (P4, 250 ng/ml). Increases in MCP-1 mRNA and protein were observed in response to TNFalpha within 24 and 48 h of culture, respectively (P < 0.05). Interferon-gamma stimulated (P < 0.05) both MCP-1 mRNA and protein after 24 h of culture, and this effect was also sustained through 48 h of culture (P < 0.05). Cotreatment of cultures with TNFalpha + IFNgamma lead to further increases (P < 0.05) in MCP-1 in both 24- and 48-h cultures. Surprisingly, neither PGF2alpha nor P4 affected MCP-1 production. Subsequent experiments revealed that the endothelial cells lacked prostaglandin F2alpha receptor mRNA, and the MAPK pathway, although present and responsive to growth factor stimulation, was unresponsive to PGF2alpha stimulation. In summary, endothelial cells derived from bovine CL respond to TNFalpha and IFNgamma stimulation with an increase in MCP-1 secretion. In contrast, neither PGF2alpha nor P4 directly influenced endothelial expression of MCP-1. These results suggest that cytokines stimulate the synthesis of MCP-1 observed during PGF2alpha-induced luteal regression.