Fleur Bossi

We monitored the number of intravascular platelet-leukocyte aggregates (PLAs) and thrombotic occlusions (TOs) by intravascular microscopy in the mesentery of rats receiving antiphospholipid (aPL) immunoglobulin G (IgG) purified from the sera of patients with antiphospholipid syndrome. aPL IgG had no procoagulant effect, but it caused rapid endothelial deposition of fibrinogen, followed by PLA and TO in rats receiving an intraperitoneal injection of bacterial lipopolysaccharide 3 hours before IgG infusion. Anti-beta2-glycoprotein I-depleted aPL IgG failed to induce PLAs and TOs. C3 and C9 colocalized with aPL IgG on the mesenteric vessels. The number of PLAs and TOs was markedly reduced in C6-deficient rats and in animals treated with anti-C5 miniantibody, suggesting the contribution of the terminal complement (C) complex to the aPL antibody-mediated intravascular thrombosis. In conclusion, our data indicate that antibodies to beta2-glycoprotein I trigger coagulation subsequent to a priming proinflammatory factor and that the terminal C complex is the main mediator of the coagulation process.

During early pregnancy, uterine mucosa decidualization is accompanied by a drastic enrichment of CD56(high)CD16(-) natural killer (NK) cells. Decidual NK (dNK) cells differ from peripheral blood NK (pbNK) cells in several ways, but their origin is still unclear. Our results demonstrate that chemokines present in the uterus can support pbNK cell migration through human endothelial and stromal decidual cells. Notably, we observed that pregnant women's pbNK cells are endowed with higher migratory ability compared with nonpregnant women's or male donors' pbNK cells. Moreover, NK cell migration through decidual stromal cells was increased when progesterone-cultured stromal cells were used as substrate, and this correlated with the ability of progesterone to up-regulate stromal cell chemokine expression. Furthermore, we demonstrate that dNK cells migrate through stromal cells using a distinct pattern of chemokines. Finally, we found that pbNK cells acquire a chemokine receptor pattern similar to that of dNK cells when they contact decidual stromal cells. Collectively these results strongly suggest that pbNK cell recruitment to the uterus contributes to the accumulation of NK cells during early pregnancy; that progesterone plays a crucial role in this event; and that pbNK cells undergo reprogramming of their chemokine receptor profile once exposed to uterine microenvironment.

The female reproductive tract harbors distinct microbial communities, as in the vagina, cervical canal, uterus, and fallopian tubes. The nature of the vaginal microbiota is well known; in contrast, the upper reproductive tract remains largely unexplored. Alteration in the uterine microbiota, which is dependent on the nutrients and hormones available to the uterus, is likely to play an important role in uterine-related diseases such as hysteromyoma, adenomyosis, and endometriosis. Uterine mucosa is an important tissue barrier whose main function is to offer protection against pathogens and other toxic factors, while maintaining a symbiotic relationship with commensal microbes. These characteristics are shared by all the mucosal tissues; however, the uterine mucosa is unique since it changes cyclically during the menstrual cycle as well as pregnancy. The immune system, besides its role in the defense process, plays crucial roles in reproduction as it ensures local immune tolerance to fetal/paternal antigens, trophoblast invasion, and vascular remodeling. The human endometrium contains a conspicuous number of immune cells, mainly Natural Killers (NK) cells, which are phenotypically distinct from peripheral cytotoxic NK cells and macrophages. The endometrium contains also few lymphoid aggregates comprising B cell and CD8+ T cells. The number and the phenotype of these cells change during the menstrual cycle. It has become evident in recent years that the immune cell phenotype and function can be influenced by microbiota. Immune cells can sense the presence of microbes through their pattern recognition receptors, setting up host-microbe interaction. The microbiota exerts an appropriately controlled defense mechanism by competing for nutrients and mucosal space with pathogens. It has recently been considered that uterus is a non-sterile compartment since it seems to possess its own microbiota. There has been an increasing interest in characterizing the nature of microbial colonization within the uterus and its apparent impact on fertility and pregnancy. This review will examine the potential relationship between the uterine microbiota and the immune cells present in the local environment.

To cite this article : Maurer M, Bader M, Bas M, Bossi F, Cicardi M, Cugno M, Howarth P, Kaplan A, Kojda G, Leeb‐Lundberg F, Lötvall J, Magerl M. New topics in bradykinin research. Allergy 2011; 66 : 1397–1406. Abstract Bradykinin has been implicated to contribute to allergic inflammation and the pathogenesis of allergic conditions. It binds to endothelial B 1 and B 2 receptors and exerts potent pharmacological and physiological effects, notably, decreased blood pressure, increased vascular permeability and the promotion of classical symptoms of inflammation such as vasodilation, hyperthermia, oedema and pain. Towards potential clinical benefit, bradykinin has also been shown to exert potent antithrombogenic, antiproliferative and antifibrogenic effects. The development of pharmacologically active substances, such as bradykinin receptor blockers, opens up new therapeutic options that require further research into bradykinin. This review presents current understanding surrounding the role of bradykinin in nonallergic angioedema and other conditions seen by allergists and emergency physicians, and its potential role as a therapeutic target.

Fetal trophoblast cells invading the decidua in the early phase of pregnancy establish complex interaction with the maternal extracellular matrix. We discovered that C1q was widely distributed in human decidual stroma in the absence of C4 and C3 and was actively synthesized by migrating extravillous trophoblasts. The cells expressed the messages for the three chains of C1q and secreted this complement component that interacted with the proteins of the decidual extracellular matrix. Solid phase-bound C1q promoted trophoblast adhesion and migration, and cell binding to C1q resulted in activation of ERK1/2 MAPKs. Ab inhibition experiments showed that the receptors for the globular head of C1q/p33 and α(4)β(1) integrin were both involved in this process and were colocalized on the cell surface following binding of C1q to trophoblasts. We also found that C1q(-/-) mice manifested increased frequency of fetal resorption, reduced fetal weight, and smaller litter sizes compared with wild-type mice. C1q deficiency was associated with impaired labyrinth development and decidual vessel remodeling. Collectively, these data suggest that C1q plays an important role in promoting trophoblast invasion of decidua and that defective local production of C1q may be involved in pregnancy disorders, such as pre-eclampsia, characterized by poor trophoblast invasion.