Migratory capacity of large granular lymphocytes from T-gamma-lymphoproliferative disorders

We have investigated 10 patients with T gamma-lymphoproliferative disorders (T gamma LPD) for cell migratory capacity. Large granular lymphocytes (LGLs) expanding in these subjects expressed natural killer cell markers (HNKI, B73.1, AB8.28, N901, OKM1) to a variable extent. The patients' LGLs mediated antibody-dependent cellular cytotoxicity, while appreciable natural killer activity was only measurable in 3 patients. The migratory capacity of T gamma LPD was examined by using nitrocellulose filters. The patients' LGLs migrated into filters and showed responsiveness (in 9 of 10 patients) to activated serum, used as chemoattractant, as normal LGLs do. No clearcut correlation emerged between in vitro migratory capacity and disease aggressiveness or involvement of abdominal organs. These results confirm in T gamma LPD the migratory potential of LGLs and suggest the possibility that acquisition of enhanced locomotor capacity is not a crucial determinant of disease aggressiveness in T gamma LPD.     

A survey of 178 NF-Y binding CCAAT boxes.

The CCAAT box is one of the most common elements in eukaryotic promoters, found in the forward or reverse orientation. Among the various DNA binding proteins that interact with this sequence, only NF-Y (CBF, HAP2/3/4/5) has been shown to absolutely require all 5 nt. Analysis of a database with 178 bona fide NF-Y binding sites in 96 unrelated promoters confirms this need and points to specific additional flanking nucleotides (C, Pu, Pu on the 5'-side and C/G, A/G, G,A/C, G on the 3'-side) required for efficient binding. The frequency of CCAAT boxes appears to be relatively higher in TATA-less promoters, particularly in the reverse ATTGG orientation. In TATA-containing promoters the CCAAT box is preferentially located in the -80/-100 region (mean position -89) and is not found nearer to the Start site than -50. In TATA-less promoters it is usually closer to the +1 signal (at -66 on average) and is sometimes present in proximity to the Cap site. The consensus and location of NF-Y binding sites parallel almost perfectly a previous general statistical study on CCAAT boxes in 502 unrelated promoters. This is an indication that NF-Y is the major, if not the sole, CCAAT box recognizing protein and that it might serve different roles in TATA-containing and TATA-less promoters.     

Induction of haptotactic migration of melanoma cells by neutrophil activating protein/interleukin-8

Natural or recombinant neutrophil activating cytokine (IL-8) induced migration across polycarbonate filters of human A 2058 melanoma cells. Anti-IL-8 antibodies blocked IL-8 induced melanoma cell migration. Checkerboard experiments revealed a gradient-dependent response of A2058 melanoma cells to IL-8. Filters exposed to IL-8 and washed supported melanoma cell migration, thus implying a haptotactic component in the response. The homologous polypeptide platelet factor 4 was inactive. The observation that IL-8 affects melanoma cells emphasizes the need for a comprehensive analysis of the spectrum of action of platelet factor 4-related peptides. The effect of the inflammatory cytokine IL-8 on melanoma cells may be relevant to augmented secondary localization of tumors at sites of inflammation.