The aetiology and cellular mechanism of chronic inflammatory processes are poorly understood. Macrophages act prominently in the inflammatory response and we report here that they express two calcium-binding proteins. The expression of these proteins, referred to as MRP-8 and MRP-14, is specific for cells of myeloid origin, namely granulocytes, monocytes and macrophages, and is observed in blood granulocytes and monocytes but not in normal tissue macrophages. In acutely inflamed tissues, macrophages can express MRP-14 but not MRP-8, and in chronic inflammations, such as primary chronic polyarthritis, infiltrate macrophages express both MRP-8 and MRP-14. Characterization of MRP-8 and MRP-14 could therefore be useful to the understanding of cellular processes induced in chronic inflammation.

Transforming growth factors /? belong to a group of cytokines that control cellular proliferation and differentiation. Five isoforms are known that share approximately 75% sequence identity, but exert different biological activities. The structure of TGF-/?3 was solved by X-ray crystallography and refined to a final R-factor of 17.5% at 2.0 A resolution. Comp~ison with the structure of TGF-02 (Schlunegger MP, Grutter MG, 1992, Nature 358430-434; Daopin S, Piez KA, Ogawa Y, Davies DR, 1992, Science 252369-373) reveals a virtually identical central core. Differences exist in the conformations of the N-terminal a-helix and in the P-sheet loops. In TGF-03, the N-terminal cu-helix has moved = 1 A away from the central core. This movement can be correlated with the mutation of Leu 17 to Val and Ala 47. to Pro in TGF-63. The /?-sheet loops rotate as a rigid body 9" around an axis that runs approximately parallel to the dimer axis. If these differences are recognized by the TGF-0 receptors, they might account for the individual cellular responses. A molecule of the precipitating agent dioxane is bound in a crystal contact, forming a hydrogen bond with Trp 32. This dioxane may occupy a carbohydrate-binding site, because dioxane possesses some structural similarity with a carbohydrate. The dioxane is in contact with two tryptophans, which are often involved in carbohydrate recognition.

We have identified a cDNA coding for a protein of 160 kDa which is expressed in in vitro cultured human peripheral blood monocytes. The predicted amino acid sequence contains an alpha‐helical rod domain possessing features characteristic of intermediate filament proteins. However, the immunocytochemical staining pattern, abundance and solubility in Triton X‐100/high salt buffers suggest that this protein is probably only associated with the intermediate filament network and represents a new type of intermediate filament associated protein. In a survey of normal, inflammatory and human tumour tissue samples, this protein, which we have named restin, was found to be highly expressed in Reed‐Sternberg cells, the tumoral cells diagnostic for Hodgkin's disease. We suggest that restin overexpression may be a contributing factor in the progression of Hodgkin's disease.

Cox and Bürk (Eur. J. Biochem., 1991) reported the partial characterization of Milk Growth Factor (MGF) which stimulated the migration of fibroblasts. We have fractionated the partially purified sample by RP-HPLC and obtained the separation of two peaks of activity. The two active components were isolated as pure MGF-a and MGF-b by RP-HPLC and preparative SDS-PAGE. The purified MGF-a, consisting of a single band by gel electrophoresis and a single peak on an HPLC reversed-phase C-4 column, has the same specific activity as TGF-beta 2 in the fibroblast migration assay. MGF-a was digested by endoprotease Asp-N and the cleaved peptides were analyzed by Edman degradation and plasma desorption mass spectrometry (PDMS). The whole sequence of MGF-a determined by automated sequenator and PDMS of S-pyridylethylated protein and selected fragments was found to be identical to that of TGF-beta 2. MGF-b protein mixture separated by SDS-PAGE was electrophoretically transferred onto a Biometra Glassybond membrane, and the blotted MGF-b protein was directly sequenced on an automated sequenator. The identified 29 amino acids sequence of MGF-b was identical to the amino-terminal sequence of TGF-beta 1. Our study demonstrates that MGF is composed of both TGF-beta 1 and TGF-beta 2. TGF-beta 2 (85%) is the predominant form.

No abstract