Consequences of neutrophil adhesion to physiological and pathological targets

The ability of neutrophils to adhere in a coordinated and reversible manner to the endothelium and other tissular components is crucial to their chemoattractant-induced locomotion towards relevant targets. Opsonins play a major role in the killing effect of neutrophils by inducing close adherence between the neutrophil and the target, thus maximizing the effect of the reactive oxygen species released by the stimulated neutrophils. Reactive oxygen species are released together with degradative enzymes and other killing proteins associated with neutrophil degranulation. This targeted neutrophil activity kills invading microorganisms but, in a similar way, may be harmful to organs, cells and molecules that have been altered in some way or are involved in immune reactions. In some other pathological situations where body fluids contain proinflammatory agents, neutrophils may behave in a nontargeted and inappropriate manner. In such cases, adherence is often increased, thus slowing locomotion. Moreover, inflammatory agents often prime neutrophils for the oxidative burst induced by chemoattractants or other stimuli. The combined slow locomotion and hypersensitivity of primed neutrophils leads to a premature release of killing substances which may affect blood components, vascular cells, connective tissue or whole organs. Any disturbance of neutrophil adherence is thus potentially harmful and must be recognized and suitably treated.     

Cerebral Vulnerability Is Associated with Selective Increase in Extracellular Glutamate Concentration in Experimental Thiamine Deficiency

Abstract: The concentration of apolipoprotein E (apoE), a high-affinity ligand for the low-density lipoprotein receptor, increases dramatically in peripheral nerve following injury. This endoneurial apoE is thought to play an important role in the redistribution of lipids from the degenerating axonal and myelin membranes to the regenerating axons and myelin sheaths. The importance of apoE in nerve repair was examined using mutant mice that lack apoE. We show that at 2 and 4 weeks following sciatic nerve crush, regenerating nerves in apoE-deficient mice were morphologically similar to regenerating nerves in control animals, indicating that apoE is not essential for peripheral nerve repair. Moreover, cholesterol synthesis was reduced in regenerating nerves of apoE-deficient mice as much as in regenerating nerves of control animals. These results suggest that the intraneural conservation and reutilization of cholesterol following nerve injury do not require apoE.     

Circadian locomotor rhythms, but not photoperiodic responses, survive surgical isolation of the SCN in hamsters.

Surgical isolation of the suprachiasmatic nuclei (SCN) within a hypothalamic island is reported to produce loss of circadian rhythmicity. The results have been interpreted to indicate that SCN efferents are necessary for the expression of circadian rhythms. It is not clear, however, whether the loss of circadian rhythms in behavioral responses following SCN isolation is attributable to transection of efferents, to loss of cells within the island, or to gliosis produced by the knife cut. To explore this issue, we examined locomotor activity and gonadal state of male golden hamsters housed in constant darkness (DD, with a dim red light for maintenance) for at least 10 weeks following isolation of the SCN from the rest of the brain by cuts by means of a Halasz wire microknife. Brain sections were immunocytochemically stained for the peptides vasoactive intestinal polypeptide (VIP), vasopressin (VP) or neurophysin II (NP II), and neuropeptide Y (NPY) to localize the SCN and to assess its viability, and for glial fibrillary acidic protein (GFAP) to delimit the border of the knife cut. Experimental animals with VIP and VP/NP II immunoreactivity in the SCN within the island retained free-running locomotor rhythms following transection of SCN efferents. Animals with cuts that failed to sever SCN efferents, and sham-operated animals (in which the Halasz knife was lowered but not rotated), also maintained circadian rhythmicity. Hamsters sustaining severe damage to the SCN showed disrupted locomotor activity. In those hamsters that retained circadian locomotor rhythmicity following SCN isolation, gonads failed to regress in DD, demonstrating the absence of an appropriate photoperiodic response. The results suggest a multiplicity of SCN coupling mechanisms in the control of circadian rhythms.     

Cellular growth modulation. I. Effects of extracellular matrix and tumor cell conditioned medium

Earlier studies reported the enzymatic modulation of the cell surface in malignant transformation of human normal mammary epithelial cells and in conversion of mammary carcinoma. Carcinoembryonic antigen (CEA) is a neoplasm-associated antigen, its production and release is used to monitor changes in cell phenotype. The present study shows that CEA production and release by human colon carcinoma (CCC), and by colon cells from patients with familial polyposia coli (FPC) and ulcerative colitis (UCC) is inhibited when the cells are cultured in contact with confluent normal colon epithelial (HNCEC) cell monolayer. Footprints left behind and/or conditioned media from HNCEC cells inhibited, whereas footprints left behind and/or conditioned media from CCC, FPC or Ucc enhanced CEA release. During sequential passages of HNCEC cells grown on footprints and/or in spent media from CCC cultures, HNCEC cells acquire the ability to produce and release CEA, and to develop tumors in athymic Nu/Nu mice. On the other hand, during sequential passages, CCC, FPC or UCC grown in spent media, or on footprints left behind HNCEC cells, showed significant decrease in CEA production and release, and in oncologic ability in athymic mice. It is concluded that both the extracellular matrix, and a growth-regulating factor(s) in the spent medium modulate cellular transformation. Quantitative data on CEA-release indicate that FPC and UCC represent an intermediary stage between normal colon epithelial cells and colon carcinoma cells, i.e. a preneoplastic stage.     

Action of adenosine triphosphate on human skin and gingival fibroblasts. Protective action of fibronectin

If cultured in media supplemented with adenosine triphosphate (ATP), EDTA, trypsin, thrombin, or incubated at 0-15 degrees C, human skin fibroblasts (HSF) and human gingival fibroblasts (HGF) change from long attached elliptical to round floating cell cultures. Also, if treated with ATP, EDTA, trypsin, thrombin, or incubated at 0-15 degrees C, the attached HFS or HGF monolayers detach from plastic substratum and form floating round cells that progressively aggregate together and die. The described experiments examined the role of cellular and extracellular ATP on HSF and HGF attachment. These two types of fibroblasts differed in their cellular ATP levels and their response to metabolic inhibitors. ATP causes destruction of microtubules as monitored by colcemid uptake and cellular detachment. Fibronectin protects both HSF and HGF from the effects of extracellular ATP.     

Structural changes occurring during transformation of the labial gland cells to their adult form,in Manduca sexta

The labial gland of the adult sphingid moth, Manduca sexta, is composed of five distinct regions, each made of a single cellular type. Four of these regions are derivatives of the single specialized cellular population that makes up the caterpillar labial duct. Both the larval labial duct and its derivatives are large, polyploid cells with pleiomorphic nuclei. There is a definite cellular continuity between the larval and adult forms of these cells throughout metamorphosis; no mitoses or cell deaths are seen to occur in the gland during transformation. Cytological studies indicate that in the process of cell transformation the ducts first “dedifferentiate,” elongate, then redifferentiate. Intermediates in this process have well defined structures which should make this system useful in studying covert events in the transformation process.