Regakine-1: An Abundant Serum Chemokine

Regakine-1, a novel CC chemokine recently identified in bovine serum, shares less than 50% identity with any known human chemokine.¹ Amino acid (aa) sequence alignment of Regakine-1 demonstrates that it is most homologous to human eotaxin. It lacks common eotaxin residues, however, shared among other species. The 7.5 kDa, 70 aa protein has weak chemotactic activity for neutrophils and lymphocytes and no chemotactic activity for monocytes or eosinophils. Thus, the identity with human eotaxin is most likely not biologically relevant.

The weak chemotactic activity of Regakine-1 appears to be compensated for by its relatively high concentration present in serum. Regakine-1 is naturally abundant in bovine serum (i.e. approximately 100 ng/mL). Other chemokines found at high levels in serum include Platelet Factor 4 (PF4/CXCL4) and Hemofiltrate CC Chemokine-1 (HCC-1/CCL14).^2,3 PF4 is synthesized by megakaryocytes and platelets and is released from alpha granules of activated platelets. HCC-1 is constitutively expressed in numerous tissues and is present at high concentrations in both normal plasma and blood from chronic renal failure patients.⁴ In contrast to many other chemokines, Regakine-1, PF4, and HCC-1 are all weak leukocyte chemoattractants.

The chemotactic effects of these serum-derived chemokines can be augmented, however, in the presence of other cytokines or chemokines. For example, a synergistic effect on neutrophil and lymphocyte chemotaxis is observed with Regakine-1 in conjunction with IL-8 or MCP-3.¹ In a similar manner, the weak neutrophil activation and eosinophil migration seen in response to PF4 can be augmented by TNF-alpha and IL-5, respectively.^5,6 The molecular mechanism(s) responsible for these synergistic effects of serum chemokines with tightly regulated cytokines, however, presents a new area for investigation. The purpose of these blood-borne chemokines may be to enhance the chemotactic effects of other chemokines or perhaps regulate leukocyte trafficking, hematopoiesis, or angiogenesis.

References

1. Struyf, S. et al. (2001) Blood 97:2197.
2. Deuel, T.F. et al. (1977) Proc. Natl. Acad. Sci. USA 74:2256.
3. Schulz-Knappe, P. et al. (1996) J. Exp. Med. 183:295.
4. Schulz-Knappe, P. et al. (1998) J. Exp. Med. 188:603.
5. Petersen, F. et al. (1996) J. Immunol. 156:1954.
6. Bruijnzeel, P.L. et al. (1993) J. Invest. Dermatol. 100:137.