Caspase Related Peptides

Definition
Cathelin-related antimicrobial peptide (CRAMP) is a family of polypeptides found in lysosomes in polymorphonuclear leukocytes (PMNs)1. They are components of innate immunity and effectively inhibit the growth of gram-negative bacteria1.

Discovery
Cathelin was first identified in pig leukocytes as a cysteine protease inhibitor2. Since then several CRAMPs with antimicrobial activity have been identified in various animals including mouse femoral marrow cells3.

Classification
CRAMPs, members of cathelicidin gene family are antimicrobial peptides that are closely related to the cathepsin family of cysteine protease inhibitors3. Over 20 members of CRAMPs have been identified.

Structural Characteristics
CRAMPs contain a highly conserved cathelin like N terminal domain and a variable antibacterial C terminal domain3.

Mode of action
Cells producing CRAMPs such as neutrophils, monocytes and macrophages are recruited at the site of bacterial infection or wound4. CRAMPs are activated by cleavage of their N terminal cathelin domains that releases their antimicrobial domain4. Once activated, it is suggested that they may neutralize lipopolysaccharide that is present on the membrane of gram-negative bacteria thus killing them4.

Functions
CRAMPs are players in host defense mechanism against microbial attacks3. They are effective antibiotics against gram-negative bacteria4. They play an important role in blocking the onset of inflammation4. They also play a role in wound repair4. It has been suggested that they may have therapeutic potential for gram-negative bacterial sepsis and septic shock4.

References
1.Ha JM, Shin SY and Kang SW (1999). Synthesis and Antibiotic Activities of CRAMP, a Cathelin-related Antimicrobial Peptide and Its Fragments. Antibiotic Activity of CRAMP and Its Fragments Bull. Korean Chem. Soc., 20 (9) 1073.
2.Ritonja A, Kopitar M, Jerala R and Turk V (1989). Primary structure of a new cysteine proteinase inhibitor from pig leucocytes. FEBS Lett. 255, 211–214.
3.Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M , Merluzzi L, and Gennaro R (1997). Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse. J Biol. Chem., 273 (20), 13088-93.
4.Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, Heumann D (2001). Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. J Immunol., 167(6), 3329-38.