The early serologic response of infants to infection with
The early serologic response of infants to infection with HIV-1 is obscured by the presence of transplacentally acquired maternal HIV antibody. However, the HIV 69 2 produced in vitro by peripheral blood from infants has been studied (Pollack et al., 1993) and it has been shown that neonatal infants can produce IgG antibodies to a restricted number of antigens suggesting that they might be infected early before birth. Studies on the distribution of possible `cofactor' receptors and CD4 early during development in humans will elucidate their potential roles in susceptibility to HIV-1 during human foetal development.
Acknowledgements We thank Ulf Pettersson for providing excellent working facilities and discussions, Ulf Eriksson for help with E9 embryos. This study was supported by the Swedish NSRC grants B-BU 8524-317, B-BU 4024-309,310; the Swedish MRC grants K93-03B-10159-02, 04X-2887; the Marianne and Marcus Wallenbergs Stiftelse; the Swedish Institute and the Marcus Borgström's Fund.
Intoduction During key biological processes such as embryonic development, tissue remodeling, restitution, and wound repair, there is a requirement for epithelial cells to escape from the rigid structural constraints provided by the tissue architecture and adopt a phenotype more amenable to cell migration and movement. The highly conserved and fundamental process that achieves this morphogenetic transformation is known as the epithelial–mesenchymal transition (EMT, reviewed in , ). Essentially, during this event, epithelial cells actively downregulate cell–cell adhesion systems, lose their polarity, and acquire a mesenchymal phenotype with reduced intercellular interactions and increased migratory capacity. As with other physiological processes that become co-opted by tumor cells, the EMT is now also widely recognized as a pathological process that contributes to cancer progression, particularly as it relates invasion and metastasis . De-differentiation, loss of adhesive constraints, enhanced motility, and invasion are all hallmarks of increased malignancy for any given tumor, and the EMT provides a mechanism for carcinoma cells to acquire this more aggressive phenotype. In fact, in some cases, it may even be critical for tumor cell survival itself . Interleukin-8 (IL-8; CXCL-8), originally described as a potent chemotactic factor for neutrophils, belongs to a superfamily of structurally related chemokines (chemotactic cytokines) that stimulate the migratory capacity of a distinct set of leukocytes, including basophils, monocytes, lymphocytes, and eosinophils (reviewed in , ). The response of leukocytes to these specialized cytokines is central to inflammatory and immunological processes. Other cell lineages, such as fibroblasts and keratinocytes, can also respond to the action of IL-8 and related peptides , . Chemokines are low molecular weight proteins with cysteines at well-conserved positions, and the CXC subclass, which contains IL-8, is distinguished by the presence of one intervening amino acid between the first two cysteine residues. The biological effects of IL-8 are mediated by two highly related chemokine receptors, CXCR-1 and CXCR-2 (also known as IL-8RA and IL-8RB, respectively) , . Both are members of a seven-transmembrane domain G-protein-coupled superfamily, and each binds IL-8 with high affinity. CXCR-2, however, is a more promiscuous receptor that can additionally bind other CXC cytokines, including growth-related oncogene (GRO) family members, neutrophil-activating peptide 2 (NAP-2), and epithelial cell-derived neutrophil attractant 78 (ENA-78) , . While many of their functions are overlapping, differences in cellular distribution, signaling responses and kinetics of receptor phosphorylation, desensitization and internalization have led to the suggestion that each of these two receptors is capable of activating distinct downstream pathways and can therefore exhibit different physiological roles .