Cathelicidins: a novel protein family with a common proregion and a variable C‐terminal antimicrobial domain

Zanetti, Margherita; Gennaro, Renato; Romeo, Domenico

doi:10.1016/0014-5793(95)01050-o

Cited by 657 publications

(544 citation statements)

References 57 publications

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“…To identify candidate cathelicidins in mouse, primers were designed against various regions within the highly evolutionarily conserved NH 2 -terminal cathelin domain of these gene products. This approach has been successful previously in identifying multiple cathelin-related genes in several species (7). Only a single cathelicidin was identified by this approach in mouse despite the use of multiple primers and tissue sources for RNA and large scale screening of more than 500 cathelinrelated clones.…”

Section: Discussionmentioning

confidence: 99%

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Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse

Gallo

Kim

Bernfield

et al. 1997

Journal of Biological Chemistry

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372

319

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Cathelicidins are the precursors of potent antimicrobial peptides that have been identified in several mammalian species. Prior work has suggested that members of this gene family can participate in host defense through their antimicrobial effects and activate mesenchymal cells during wound repair. To permit further study of these proteins a reverse transcriptase-polymerase chain reaction approach was used to identify potential mouse homologs. A full-length 562-base pair cDNA clone was obtained encoding an NH 2 -terminal prepro domain homologous to other cathelicidins and a unique COOH-terminal peptide. This gene, named Cramp for cathelin-related antimicrobial peptide, was mapped to chromosome 9 at a region of conserved synteny to which genes for cathelicidins have been mapped in pig and man. Northern blot analysis detected a 1-kilobase transcript that was expressed in adult bone marrow and during embryogenesis as early as E12, the earliest stage of blood development. Reverse transcriptase-polymerase chain reaction also detected CRAMP expression in adult testis, spleen, stomach, and intestine but not in brain, liver, heart, or skeletal muscle. To evaluate further the expression and function of CRAMP, a peptide corresponding to the predicted COOH-terminal region was synthesized. CD spectral analysis showed that CRAMP will form an amphipathic ␣-helix similar to other antimicrobial peptides. Functional studies showed CRAMP to be a potent antibiotic against Gram-negative bacteria by inhibiting growth of a variety of bacterial strains (minimum inhibitory concentrations 0.5-8.0 M) and by permeabilizing the inner membrane of Escherichia coli directly at 1 M. Antiserum against CRAMP revealed abundant expression in myeloid precursors and neutrophils. Thus, CRAMP represents the first antibiotic peptide found in cells of myeloid lineage in the mouse. These data suggest that inflammatory cells in the mouse can use a nonoxidative mechanism for microbial killing and permit use of the mouse to study the role such peptides play in host defense and wound repair.

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Section: Discussionmentioning

confidence: 99%

“…Cathelicidins have been identified in several species including pig, cow, sheep, rabbit, and man (6 -13). The high degree of conservation of their cathelin domain suggests that the members of this family evolved from a common ancestor gene through duplication and modification (7). In general, the precursors of these peptides are stored in neutrophil granules.…”

mentioning

confidence: 99%

Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse

Gallo

Kim

Bernfield

et al. 1997

Journal of Biological Chemistry

Self Cite

372

319

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“…Cathelicidins are one family of HDP characterized by conserved pro-peptide sequences, which have been identified in several mammalian species. 9 hCAP-18/LL-37 is the only antimicrobial peptide of the cathelicidin family identified in humans. It has been detected in leukocytes, such as neutrophils, monocytes, NK cells, gd cells, B cells and in the epithelial cells of the testis, the gastrointestinal and respiratory tracts and in inflamed skin as an inactive pro form.…”

Section: Introductionmentioning

confidence: 99%

Transient cutaneous adenoviral gene therapy with human host defense peptide hCAP-18/LL-37 is effective for the treatment of burn wound infections

et al. 2005

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“…The preproprotein belongs to the cathelicidin protein family. The common nominator of this protein family is a well conserved proregion of cathelin type, whereas the C-terminal domain is represented by highly variant antibacterial peptides (10). A pronounced variation is also noticed in different numbers of cathelicidin genes between mammalian species.…”

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confidence: 99%

The Expression of the Gene Coding for the Antibacterial Peptide LL-37 Is Induced in Human Keratinocytes during Inflammatory Disorders

Frohm

Agerberth

Ahangari

et al. 1997

Journal of Biological Chemistry

724

624

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The epithelia constitute a major barrier to the environment and provide the first line of defense against invading microbes. Antimicrobial peptides are emerging as participants in the defense system of epithelial barriers in general. Originally we isolated the human antimicrobial peptide LL-37 from granulocytes. The gene (CAMP or cathelicidin antimicrobial peptide) coding for this peptide belongs to the cathelicidin family, whose members contain a conserved pro-part of the cathelin type. The human genome seems to have only one gene of this family, whereas some mammalian species have several cathelicidin genes. In the present work we demonstrate up-regulation of this human cathelicidin gene in inflammatory skin disorders, whereas in normal skin no induction was found. By in situ hybridization and immunohistochemistry the transcript and the peptide were located in keratinocytes throughout the epidermis of the inflammatory regions. In addition, the peptide was detected in partially pure fractions derived from psoriatic scales by immunoblotting. These fractions also exhibited antibacterial activity. We propose a protective role for LL-37, when the integrity of the skin barrier is damaged, participating in the first line of defense, and preventing local infection and systemic invasion of microbes.Epithelia provide a barrier between the body and the environment. In addition, the epithelial cells have an active immunological role with antigen processing and presentation and production of cytokines and defense effector molecules such as microbicidal peptides. Thus, the epithelia mediate an active protection against invading microbes (1).Several broad spectrum microbicidal peptides have been identified in mammalian mucosal epithelium; bovine tracheal mucosa produces a ␤-defensin, TAP (tracheal antimicrobial peptide) (2), paneth cells of the gastrointestinal mucosa of human and mouse synthesize defensins (3, 4), and another ␤-defensin, LAP (lingual antimicrobial peptide) is expressed by bovine tongue epithelial cells (5). Thus, peptide antibiotics appear at the surface epithelium where they are likely to act as key components in the first line of defense and in the wound healing process (5). So far, all mammalian antimicrobial peptides identified at the mucosal interface belong to the defensin family. Defensins are cysteine-rich peptides folded in ␤-pleated sheets with a broad activity against bacteria, enveloped viruses, fungi, and parasites (6).We have isolated a clone for a novel human antibacterial peptide and named the putative peptide FALL-39 (7). Recently the mature active peptide LL-37 (two amino acids shorter at the N terminus than the putative peptide) was isolated from granulocytes and characterized (amino acid sequence is shown in Fig. 2B) (8). The preproprotein of LL-37 has also been named human CAP18 by another group (9). In contrast to the defensins, LL-37 is a cysteine-free peptide that can adopt an amphipathic ␣-helical conformation. The preproprotein belongs to the cathelicidin protein family. The common...

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Cathelicidins: a novel protein family with a common proregion and a variable C‐terminal antimicrobial domain

Cited by 657 publications

References 57 publications

Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse

Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse

Transient cutaneous adenoviral gene therapy with human host defense peptide hCAP-18/LL-37 is effective for the treatment of burn wound infections

The Expression of the Gene Coding for the Antibacterial Peptide LL-37 Is Induced in Human Keratinocytes during Inflammatory Disorders

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