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.

Recently, a class of protein antigens of high relative molecular mass (Mt) which can induce protective immunity against blood-stage malaria has been identified. In Plasmodium falciparum the protein has a Mr of approximately 195,000 (P195). It is the precursor of three proteins of Mr 83,000 (83K), 42K and 19K which are the major surface antigens of merozoites; thus it may also be useful for immunization against P. falciparum. Three studies describing the isolation of single short complementary DNA clones for part of the P195 gene sequence have been reported. Here we describe the complete structure of the P195 gene determined from further DNA clones, its organization within genomic DNA and the location of the specific processing fragments within the primary amino-acid sequence.

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Eighteen cDNA clones containing inserts specific for the third component of complement (C3) have been derived from high molecular weight mouse liver mRNA. The inserts span 4,600 nucleotides of the C3 coding sequence, including the 3' end ofC3 mRNA. The length of C3 mRNA was determined to be 5,100 ± 200 nucleotides, including a poly(A)-containing tail of mean length 170 nucleotides. From cDNA sequence analysis of the 5'-proximal region of C3 mRNA, the NH2-terminal amino acid sequence of the mature C3fi chain was predicted to be Ile-Pro-MetTyr-Ser-Ile-Ile-Thr-Pro-Asn-Val-Leu-Arg-Leu-Glu. This sequence is in good agreement with the reported amino acid sequences of human and guinea pig C3,B chains. These data position the C3,B subunit to the NH2-terminal portion of the precursor.C3 molecule (pro-C3) and establish the order of subunits in pro-C3 to be NHw-f3S-a-COOH. In additionl, the cDNA sequence indicates that an NH2-terminal extension peptide precedes the 13 chain in pro-C3. The amino acid sequence of the mouse C3a fragment and its flanking regions was determined. The data indicate the presence of four arginine residues located between the COOH terminus of the C31 and the NH2 terminus of the C3a subunits in pro-C3. The coding sequences of-the amino acids that constitute the internal thioester domain in C3 were determined. Unexpectedly, the glutamyl residue that has been shown to participate in the thioester bond in native C3 was found to be encoded as a glutamine.Complement is a group of interacting proteins, present in the blood of all vertebrates, that plays an essential part in the defense against microbial infections. Although the system is capable ofdirect killing and lysis ofmicroorganisms in the absence ofspecific antibodies, complement also acts as an effector ofthe humoral. immune response. The third component of complement, C3, is the central element in both the classical and the alternative pathways of complement activation. C3 contains specific sites of interaction for the classical pathway convertase C4b,2a, the alternative pathway convertase C3b,Bb, and the control proteins ,B1H and C3b inactivator. The protein is present in plasma as a two-chain molecule with disulfide-linked subunits a (Mr7 115,000) and ( (Mr) 75,000) (for review, see refs.1 and 2). C3 is synthesized as a single-chain precursor, pro-C3 (3, 4). Upon proteolytic activation by C3 convertases, C3 is cleaved into the fragments C3a (Mr, 9,000) and C3b (Mr, 180,000). C3a has anaphylactic activity and mediates inflammatory responses (5, 6). C3b has been shown to bind covalently (7) to the surfaces of foreign particles by means of a transacylation reaction (8) involving a unique structure in the C3 molecule, an internal thioester bond (9). Particle-bound C3b is cleaved by specific proteolysis into fragments C3c and C3d. The latter remains bound to the particle surface (10) and contains the thioester region (11). Clearance of C3b-coated particles by phagocytic cells involves interactions between specific cellular C3-receptor protei...