The rat chemokines CINC (cytokine-induced neutrophil chemoattractant)-1, CINC-2 alpha, CINC-2 beta and CINC-3 (also named MIP-2) constitute a group of rat CXC chemokines that show significant sequence similarity to human GROs and mouse MIP-2 but not IL-8. CINC-2 alpha, CINC-2 beta were originally purified as novel neutrophil chemoattractants from the conditioned medium of rat granulation tissue which also contain CINC-1 and CINC-3. Based on amino acid (aa) sequence analysis of the purified CINC-2 alpha protein and sequencing of the CINC-2 beta cDNA clone, both mature CINC-2 alpha and CINC-2 beta were shown to contain 68 aa residues. The amino acid sequences of the two CINC-2 proteins are identical except for three carboxy-terminal residues. CINC-2 beta cDNA encodes a 100 aa residue precursor protein with a 32 aa residue signal peptide that is removed to yield the mature secreted protein. At the protein sequence level, mature CINC-2 proteins are 63% identical to CINC-1 and 80% identical to CINC-3. CINC-2 proteins represent the major chemokines purified from conditioned medium of granulation tissue or LPS-induced inflammatory exudate. Other cell types known to produce CINC-2 proteins include activated macrophages and fibroblasts.
Recombinant and natural CINC-2 proteins have been shown to be specific neutrophil chemoattractants both in vivo and in vitro. On the basis of cross-desensitization results of the various CINC proteins, it has been postulated that rat neutrophils have at least two classes of CINC receptors: a class of CINC-3-specific receptor as well as a second common receptor shared by all CINCs.
