Adhesion of a chicken myeloblast cell line to fibrinogen and vitronectin through a beta 1-class integrin.

The adhesive interactions of circulating blood cells are tightly regulated, receptor-mediated events. To establish a model for studies on regulation of cell adhesion, we have examined the adhesive properties of the HD11 chick myeloblast cell line. Function-perturbing antibodies were used to show that integrins containing the beta 1 subunit mediate HD11 cell attachment to several distinct extracellular matrix proteins, specifically fibronectin, collagen, vitronectin, and fibrinogen. This is the first evidence that an integrin heterodimer in the beta 1 family functions as a receptor for fibrinogen. While the alpha v beta 1 heterodimer has been shown to function as a vitronectin receptor on some cells, this heterodimer could not be detected on HD11 cells. Instead, results suggest that the beta 1 subunit associates with different, unidentified alpha subunit(s) to form receptors for vitronectin and fibrinogen. Results using function-blocking antibodies also demonstrate that on these cells, additional receptors for vitronectin are formed by alpha v beta 3 and alpha v associated with an unidentified 100-kD beta subunit. The adhesive interactions of HD11 cells with these extracellular matrix ligands were shown to be regulated by lipopolysaccharide treatment, making the HD11 cell line attractive for studies of mechanisms regulating cell adhesion. In contrast to primary macrophage which rapidly exhibit enhanced adhesion to laminin and collagen upon activation, activated HD11 cells exhibited reduced adhesion to most extracellular matrix constituents

Stress-induced in vivo recruitment of human cytotoxic natural killer cells favors subsets with distinct receptor profiles and associates with increased epinephrine levels

Acute stress drives a 'high-alert' response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans. 3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH), or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells. MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment. The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats

Accept or refuse? Factors influencing the decision-making of transplant surgeons who are offered a pancreas: results of a qualitative study

Background Most offered pancreases are not transplanted. This study investigates the factors that inform and influence the transplant surgeon’s decision to select an offered pancreas. Methods Semi-standardized interviews were conducted with 14 highly qualified transplant surgeons from all 14 German transplant centers performing > 5 pancreas transplantations per year. The interviews focused on medical and non-medical criteria on which the individual accept/refuse decision depends. Interviews were recorded, transcribed and underwent content analysis. Results The interviewees agreed upon certain main selection criteria, e.g. donor age, lab results, ICU stay. However, there was no consistency in judging these parameters, and clear cut-offs did not exist. The pancreas macroscopy is a pivotal factor, as well as knowing (and trusting) the donor surgeon. 3/14 surgeons reported that they had occasionally refused a pancreas because of staff shortage. Some interviewees followed a restrictive acceptance policy, whereas others preferred to accept almost any pancreas and inspect it personally before deciding. Conclusion The assessment of medical donor characteristics is highly inconsistent. Both very cautious as well as very permissive acceptance policies may render the allocation process less efficient. A more standardized policy should be discussed. Finally, better training for donor surgeons seems advisable, in order to increase trust and thus pancreas utilization. Keywords: Pancreas transplantation; Under-utilization; Allocation process; Refusa