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...

Fluid from a post-operative wound, six leg ulcers and a large blister were collected and analysed by biochemical, microbiological and immunological techniques. The results were compared with those from sera. All samples were lyophilized and extracted twice with 60% aqueous acetonitrile containing 1 % trifluoroacetic acid. The pooled supernatants were lyophilized, redissolved, and the fluid extracts were characterized by six techniques (the blister exudate only with three) : reverse-phase HPLC, Edman degradation, mass spectrometry, Western blot analysis, inhibition zone assay on plates with Bacillus megaterium (anti-Bm activity) and zone clearing on plates with cell walls from Micrococcus luteus (a lysozyme assay). The material corresponding to HPLC peaks of the wound fluid extract was identified as: histone H2B fragments 1 -11,l-15 and 1 -16, intact thymosin p-4, defensins HNPl, 2 and 3, lysozyme and the peptide antibiotic FALL-39 and its precursor(s). The HPLC-separated blister fluid was extremely rich in anti-Bm activity (mainly defensins) and lysozyme. It may also contttin factors not identified before. The plate assays scored 50-fold differences in anti-Bm activities and more than 10-fold differences in lysozyme, factors which together with thymosin could be active in wound healing. It is concluded that analysis of wound fluid yields peptide and activity patterns with novel fragments of important peptides, and quantitative differences, that can be useful to understand molecular mechanisms of wound healing further.